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Biomedical subjects

J B Whitfield

Publications and source records attributed to J B Whitfield.

At least 37 records · Page 2Linked to original sources
PubMed1998

Phylogeny and evolution of host-parasitoid interactions in hymenoptera.

Recent studies of hymenopteran phylogeny using both comparative morphology and DNA sequence data have greatly enhanced our understanding of the evolution of that order. Resulting phylogenetic hypotheses make possible more rigorous investigations of the evolution of various biological life-styles, among them the parasitoid habit. This paper reviews the current findings from higher-taxon phylogenetic analyses of the order. A "consensus" phylogeny derived from these findings is used to trace the most likely evolutionary pathways leading to the current diversity of parasitoid habits. Taxa and biological phenomena for which our current understanding is fragmentary are highlighted. Based on current evidence, it appears that parasitism arose, from mycophagous ancestors, a single time within the order. Many subsequent elaborations of the parasitic mode of life (e.g. endoparasitism, secondary phytophagy, etc) apparently evolved independently more than once.

Animals↗
PubMed1998

Molecular biology of alcohol dependence, a complex polygenic disorder.

Alcohol dependence, and the medical conditions which arise from prolonged excessive alcohol use, have no single cause. Like other complex diseases, they result from a combination of social, personal and genetic contributions; but within any society genetic variation has a substantial influence on individual risk. The genes presently known to affect alcohol dependence produce variation in alcohol metabolism; other genes which affect personality or susceptibility to intoxication are likely to be significant but so far reproducible evidence is scanty. Designs which include related subjects have advantages for the study of complex diseases, because any association effects can be placed in the context of overall heritability and because linkage analysis can also be included. Examples of our studies of alcohol metabolism, consumption and dependence are presented.

Adult↗
PubMed1998

ADH genotypes and alcohol use and dependence in Europeans.

We have tested for effects of alcohol dehydrogenase (ADH) genotypes on self-reported alcohol consumption and symptoms of alcohol dependence, recorded on three occasions up to 15 years apart, in 377 male and female subjects of European descent. ADH2 genotype had significant effects on both consumption and dependence in the men, but not in the women. The effects of ADH3 genotype were considerably less than those of ADH2, but significant results could be demonstrated when the combined genotypes were considered. The direction of the effects on alcohol consumption and dependence risk were consistent with reports on Asian subjects, and with the in vitro properties of ADH isoenzymes. As with previous studies on the relationship between ADH type and alcohol use, population stratification cannot be excluded as a contributing factor in these results.

Adolescent↗
PubMed1998

Smoking, obesity, and hypertension alter the dose-response curve and test sensitivity of carbohydrate-deficient transferrin as a marker of alcohol intake.

Serum carbohydrate-deficient transferrin (CDT) is a specific and comparatively sensitive marker of excessive alcohol use; however, reports of its sensitivity vary according to the population or patient groups studied and their average alcohol intake. We have characterized the dose-response curve between alcohol intake and CDT concentrations in a study of 1400 men and women from a community-based twin registry. Our results show that mean CDT increases with increasing reported alcohol consumption even within the range of alcohol use considered to be nonhazardous. We found significant effects of sex, age, smoking, previous alcohol dependence, body mass index, and diastolic hypertension on the alcohol-CDT dose-response curve. These variables either affect test sensitivity or require adjustment of reference intervals. The results also provide insight into the physiological and biochemical factors that affect CDT concentration.

Adult↗
PubMed1997

Genetic and environmental contributions to alcohol dependence risk in a national twin sample: consistency of findings in women and men.

BACKGROUND: Genetic influences on alcoholism risk are well-documented in men, but uncertain in women. We tested for gender differences in genetic influences on, and risk-factors for, DSM-III-R alcohol dependence (AD). METHOD: Diagnostic follow-up interviews were conducted in 1992-3 by telephone with twins from an Australian twin panel first surveyed in 1980-82 (N = 5889 respondents). Data were analysed using logistic regression models. RESULTS: Significantly higher twin pair concordances were observed in MZ compared to DZ same-sex twin pairs in women and men, even when data were weighted to adjust for over-representation of well-educated respondents, and for selective attrition. AD risk was increased in younger birth cohorts, in Catholic males or women reporting no religious affiliation, in those reporting a history of conduct disorder or major depression and in those with high Neuroticism, Social Non-conformity, Toughmindedness, Novelty-Seeking or (in women only) Extraversion scores; and decreased in 'Other Protestants', weekly church attenders, and university-educated males. Controlling for these variables, however, did not remove the significant association with having an alcoholic MZ co-twin, implying that much of the genetic influence on AD risk remained unexplained. No significant gender difference in the genetic variance in AD was found (64% heritability, 95% confidence interval 32-73%). CONCLUSIONS: Genetic risk-factors play as important a role in determining AD risk in women as in men. With the exception of certain sociocultural variables such as religious affiliation, the same personality, sociodemographic and axis I correlates of alcoholism risk are observed in women and men.

Adult↗
PubMed1996

Alcohol reactions in subjects of European descent: effects on alcohol use and on physical and psychomotor responses to alcohol.

Self-reports of reactions to small amounts of alcohol, obtained between 1990 and 1992, were compared with reports of alcohol use, obtained in 1990-1992 and also in 1979-1981, in twin subjects of European descent. Data on subjective, physiological, psychomotor, and metabolic responses to a test dose of alcohol, taken in 1979-1981, were also available. Alcohol reactions were more common in women than in men, and were associated with less alcohol use, both at the time that information about reactions was obtained and as recorded on average 12 years previously, in both sexes. Physiological and psychomotor responses to alcohol were similar across the reaction groups, except that deterioration in standing steadiness was greater in those who subsequently reported adverse reactions to alcohol. Contrary to expectation, skin temperature changes after alcohol were less in the subjects who reported always reacting to alcohol than in the other groups. Subjective reports of intoxication were greatest in subjects who subsequently reported alcohol reactions. The pattern of twin pair concordance for reactions suggests low heritability, so alcohol reactions in subjects of European descent are not caused by a single gene of high penetrance of the type found in the Asian alcohol flush reaction.

Adult↗
PubMed1995

Is alcohol-related flushing a protective factor for alcoholism in Caucasians?

Although alcohol-related flushing seems to be a genetically influenced protective factor for alcoholism in some Asian groups, little is known about whether this is true for Caucasians. The evidence for alcohol-related flushing as a protective factor for the development of alcoholism was examined in a sample of 5831 Australian twins (2041 men, 3790 women) who were administered a structured psychiatric interview. Twin correlations for self-reported adverse alcohol reactions (e.g., "flushing or blushing" and "feeling very sleepy" after drinking 1 or 2 drinks) were modest, suggesting minimal contribution of genetic factors, but when corrected for reliability of measurement, were consistent with moderate heritabilities. In accord with studies examining Asian samples, we found that individuals who experienced adverse reactions after drinking small amounts of alcohol drank less often and slightly less per drinking occasion than those who did not experience adverse reactions. However, those who experienced adverse reactions were more likely to have symptoms of alcoholism and to report a parental history of alcohol problems. We conclude that self-reported alcohol-related flushing is not a protective factor for alcoholism in Caucasians and may be a risk factor.

Adult↗
PubMed1995

Alcohol sensitivity and smoking history in men and women.

Many studies have found genetic effects to contribute to alcoholism risk in both men and women. Based on preliminary evidence for shared genetic risk between smoking and drinking problems, a reanalysis of alcohol challenge data on 412 Australian twins was performed to explore the possibility that smoking may diminish or moderate the intoxicating effects of alcohol. We found history of smoking to be strongly associated with self-reported intoxication after alcohol challenge in women (women: r = -0.44 +/- 0.08; men: r = -0.21 +/- 0.08), comparable with self-reported average weekly consumption of alcohol, which was more strongly associated in men (women: r = -0.37 +/- 0.07; men: r = -0.54 +/- 0.06). Structural equation model-fitting indicated a strong association between heavy drinking and smoking, but the association between smoking and postalcohol intoxication remained even when the effects of heavy drinking were controlled for. These results prompt the question of whether smoking cigarettes directly influences the transition from moderate to excessive use of alcohol by diminishing feelings of alcohol intoxication.

Adolescent↗
PubMed1995

Diagnostic tests for alcohol consumption.

A variety of laboratory tests are available to assist in the diagnosis of hazardous alcohol consumption and related disorders. Standard tests, such as serum gamma glutamyltransferase activity and erythrocyte mean cell volume, have limited sensitivity, particularly in detecting non-dependent hazardous consumption. Most also have poor specificity in that results are affected by common diseases and medications. Over the past 10 years a number of new laboratory tests have emerged. One of these, carbohydrate deficient transferrin, has high sensitivity in detecting persons with alcohol dependence, and shows promise for identification of non-dependent hazardous drinking; it is also highly specific. Others such as measurement of bound acetaldehyde, serum beta-hexosaminidase and the ratio of urinary serotonin metabolites offer promise in detecting recent heavy drinking. However, many issues remain unresolved. The newer markers have often been judged by contrasting their values in patients who are clearly alcohol dependent and abstainers or very light drinkers. It is now apparent that some are relatively insensitive markers of hazardous consumption. Future research needs to examine the performance of these markers among subjects with a range of alcohol intakes to fully determine their value in assessing drinking history. In addition, assays which are capable of some degree of automation need to be developed for analysing large numbers of samples.

Alanine Transaminase↗
PubMed1995

Carbohydrate deficient transferrin levels in hazardous alcohol consumption.

Little information is available on the value of carbohydrate deficient transferrin (CDT) in detecting persons with hazardous alcohol consumption. In the present study isoelectric focusing (IEF) and immunofixation were used to examine the sensitivity of CDT in hazardous drinkers compared with control subjects and alcohol dependent persons. Elevated CDT levels (> 100 mg/l) were found in 62% of hazardous drinkers and 67% of alcohol dependent persons compared with only 5% of controls. CDT was more sensitive than serum gamma glutamyltransferase (GGT) activity in detecting hazardous alcohol consumption (sensitivity of GGT 19%; P < 0.001), but was of comparable sensitivity to GGT for alcohol dependence. Neither the transferrin index nor transferrin ratio offered any advantage over CDT in detecting hazardous consumption. We conclude that serum CDT, as measured by IEF and immunofixation, is a sensitive and specific test for hazardous drinking.

Adult↗
PubMed1994

Alcohol consumption and alcohol pharmacokinetics: interactions within the normal population.

We have analyzed the interrelationships between habitual alcohol consumption, peak blood alcohol concentration after a standard dose, and rate of alcohol metabolism in a group of 199 male and 213 female twins. Both peak concentration and rate of metabolism are strongly associated with alcohol consumption levels, even in the range of 0-10 g of alcohol/day. The peak concentration and rate of metabolism were strongly correlated in both men and women; this is not due to their common dependence on alcohol intake nor to experimental error. These results show that the threshold for effects of habitual consumption on alcohol pharmacokinetics is much lower than previously suspected, and that there are factors that reduce preabsorptive or first-pass metabolism but increase postabsorptive metabolism.

Adolescent↗
PubMed1994

Genetic effects on alcohol consumption patterns and problems in women.

We review evidence that genetic factors play no less important a role in the etiology of alcoholism in women than in men. Potential mediators of this genetic influence (differences in personality or alcohol sensitivity) exhibit equal heritability in men and women. Genetically determined differences in alcohol preference (or consumption level), a phenotype widely used in animal models of alcoholism, have been neglected as a mechanism of alcoholism inheritance. Using data from the 1992-3 interview survey of the Australian twin panel (N = 5995 twins), we have reexamined the mediating role of personality and alcohol consumption variables. By comparing the non-alcoholic co-twins of alcoholic twins, and twins from concordant unaffected pairs (separately for MZ and DZ pairs), we have avoided the problem of obtaining consumption and personality assessments that are contaminated by history of alcoholism. In MZ pairs, in both genders, co-twin's heavy alcohol exposure (drinking 5+ drinks in one day) and co-twin's Novelty Seeking score, are both predictive of alcoholism in the respondent. The effect of co-twin's heavy alcohol exposure remains significant even when the respondent's personality variables are controlled for, implying that there are genetic effects on alcoholism risk mediated through consumption pattern that are independent of those mediated through personality differences.

Alcohol Drinking↗
PubMed1994

ADH and ALDH genotypes in relation to alcohol metabolic rate and sensitivity.

Variation in alcohol-metabolising enzymes has been proposed as an explanation for variation in alcohol use and the effects of alcohol, and the elucidation of the effects of ALDH deficiency in Asians has reinforced this view. This paper examines evidence on the relevance of ALDH and ADH variation in people of European descent, in relation to reactions to alcohol which affect alcohol use and to variation in alcohol pharmacokinetics. Genetic variation in ALDH does not explain subjects' self-reported reactions to alcohol. The known genetic variation in ADH2 has a significant effect on blood alcohol concentrations after a standard dose of ethanol but this occurs through an effect on the peak level rather than the rate of metabolism, and the ADH3 polymorphism has no effect. The substantial genetic variation in alcohol pharmacokinetics must be due to other genes, and strategies to locate and identify them are becoming available.

Alcohol Dehydrogenase↗
PubMed1993

Aversive reactions and alcohol use in Europeans.

Two hundred subjects of European descent completed a questionnaire about alcohol use and reactions to alcohol. Eleven subjects (5.5%) reported that they always experienced unpleasant reactions after small amounts of alcohol, and these subjects reported significantly lower levels for quantity and frequency of habitual alcohol use, and fewer drinks in the preceding 7 days, than the other subjects. Reactions to alcohol, either genetic or acquired, can therefore be significant in determining alcohol use in non-Asian groups.

Acetaldehyde↗
PubMed1993

Prediction of alcohol-related harm by laboratory test results.

We examined the value of laboratory markers of excessive alcohol (ethanol) intake as predictors of mortality, morbidity, and health-care utilization in a cohort of 330 patients attending an acute ambulatory care service. Among men, all four markers examined--gamma-glutamyltransferase (GGT) and aspartate aminotransferase (AST) activities, high-density lipoprotein cholesterol (HDL-C), and mean corpuscular volume (MCV)--were predictive of medical sequelae and health-care utilization over a 3-year period. In contrast, social problems were more closely related to the amount of alcohol consumption at initial assessment than to any biological marker. Serum GGT and AST activities and MCV were predictive of medical sequelae in women. The predictive value of GGT was an independent risk factor and did not merely reflect recent alcohol intake or the presence of chronic liver disease. We conclude that these readily available laboratory tests provide important prognostic information and should be an integral part of the assessment of persons with hazardous alcohol consumption.

Alcoholism↗
PubMed1993

Studies on the chronopharmacology of ethanol.

Male subjects (n = 10) were given ethanol (0.75 g/kg) at four equally spaced times in the 24 hr cycle (9 am, 3 pm, 9 pm 3 am) in random order. Blood ethanol concentrations were monitored by breath analysis and measurements were made of the blood or plasma levels of ethanol, acetaldehyde, acetate, pyruvate, lactate and cortisol. Blood pressure, heart rate and body temperature were measured before and at 60 and 120 min after ethanol administration and the effects of ethanol on a number of behavioural parameters and mood were studied. After ethanol ingestion, there was a significant decrease in body temperature, systolic blood pressure, plasma cortisol and pyruvate levels, whilst acetate levels and the lactate:pyruvate ratio were significantly increased. Standing steadiness, critical flicker fusion threshold and divided attention tracking control were significantly impaired under ethanol and self-report data indicated a significant decrease in alertness, co-ordination, concentration and attentiveness. Although a significantly higher peak blood ethanol concentration was attained at the 9 am session, other time-of-day differences did not reach significance and the pharmacokinetics of ethanol were essentially unchanged. Since the only significant diurnal variations in the response to ethanol identified in this study (apart from the subjective results) were for plasma cortisol concentrations and body temperature (both of which are well known to exhibit diurnal rhythmicity), it appears that major circadian variability in the metabolic and/or behavioural effects of ethanol is unlikely to occur.

Adolescent↗