Biomedical subjects

Boris Tabakoff

Publications and source records attributed to Boris Tabakoff.

23 records · Page 2Linked to original sources

PubMed2002

CDT, GGT, and AST as markers of alcohol use: the WHO/ISBRA collaborative project.

BACKGROUND: Estimates of the performance of carbohydrate deficient transferrin (CDT) and gamma glutamyltransferase (GGT) as markers of alcohol consumption have varied widely. Studies have differed in design and subject characteristics. The WHO/ISBRA Collaborative Study allows assessment and comparison of CDT, GGT, and aspartate aminotransferase (AST) as markers of drinking in a large, well-characterized, multicenter sample. METHODS: A total of 1863 subjects were recruited from five countries (Australia, Brazil, Canada, Finland, and Japan). Recruitment was stratified by alcohol use, age, and sex. Demographic characteristics, alcohol consumption, and presence of ICD-10 dependence were recorded using an interview schedule based on the AUDADIS. CDT was assayed using CDTect and GGT and AST by standard methods. Statistical techniques included receiver operating characteristic (ROC) analysis. Multiple regression was used to measure the impact of factors other than alcohol on test performance. RESULTS: CDT and GGT had comparable performance on ROC analysis, with AST performing slightly less well. CDT was a slightly but significantly better marker of high-risk consumption in men. All were more effective for detection of high-risk rather than intermediate-risk drinking. CDT and GGT levels were influenced by body mass index, sex, age, and smoking status. CONCLUSIONS: CDT was little better than GGT in detecting high- or intermediate-risk alcohol consumption in this large, multicenter, predominantly community-based sample. As the two tests are relatively independent of each other, their combination is likely to provide better performance than either test alone. Test interpretation should take account sex, age, and body mass index.

Adolescent↗

PubMed2002

WHO/ISBRA Study on State and Trait Markers of Alcohol Use and Dependence: analysis of demographic, behavioral, physiologic, and drinking variables that contribute to dependence and seeking treatment. International Society on Biomedical Research on Alcoholism.

BACKGROUND: Discussions between the World Health Organization (WHO) and the International Society on Biomedical Research on Alcoholism (ISBRA) identified the need for a multiple-center international study on state and trait markers of alcohol abuse and alcohol dependence. The reasoning behind the generation of such a project included the need to understand the alcohol use characteristics of diverse populations and the performance of biological markers of alcohol use in a variety of settings throughout the world. A second major reason for initiating this study was to collect DNA for well-structured and stratified association studies between genetic markers and/or "candidate" genes and behavioral/physiological phenotypes of importance to predisposition to alcohol dependence. METHODS: An extensive interview instrument was developed with leadership from the U.S. National Institute on Alcohol Abuse and Alcoholism (NIAAA). The instrument was translated from English to Finnish, French, German, Japanese, and Portuguese (Brazilian). One thousand eight hundred sixty-three subjects were recruited at five clinical centers (Montreal, Canada; Helsinki, Finland; Sapporo, Japan; São Paulo, Brazil; and Sydney, Australia). The subjects responded to the structured interview and provided blood and urine samples for biochemical analysis. This article focuses on the demographic characteristics of the study subjects, their drinking habits, alcohol-dependence characteristics, comorbid psychiatric and other drug variables, and predictors for seeking treatment for alcohol dependence. Multiple logistic regression models were constructed and used to explore variables that contribute to various levels of alcohol consumption, to a diagnosis of alcohol dependence, and to seeking treatment for alcohol dependence. ANOVA with post hoc comparisons, chi2, and Pearson moment calculations were used as necessary to assess additional relationships between variables. RESULTS: A number of factors previously noted in disparate studies were confirmed in our analysis. Men consumed more alcohol than women, Asians consumed less alcohol than whites or Blacks, alcohol-dependent subjects consumed more alcohol than nondependent subjects, alcohol consumption increased with age, and an increased level of education (university or postgraduate education) reduced the percentage of such individuals in the category designated as heavy drinkers (>210 g alcohol/week) and in the group who were currently in treatment for dependence. However, our analysis allowed for much more detailed comparisons; for example, although men drank more than women on a g/day basis, the differences were less pronounced on g/kg/day basis, and alcohol-dependent women drank equal amounts of alcohol as alcohol-dependent men on a g/kg/day basis. Antisocial personality characteristics or reports of trouble sleeping when an individual stops drinking were associated with higher alcohol intake. The most important of the tested factors that contributed to a DSM-IV diagnosis of dependence, however, was the report of anxiety if an individual stopped drinking. In terms of the various criteria within the DSM-IV criteria for alcohol dependence, no one criterion seemed to be prominent for individuals who sought alcohol dependence treatment, but the higher the number of criteria met by the individual, the higher was the probability that he or she would be in treatment. CONCLUSIONS: This initial report is the beginning of the "data mining" of this rich data set. The cross-national/cross-cultural aspects of this study allowed for multiple comparisons of variables across several ethnic/racial groups and allowed for assessment of biochemical markers for alcohol intake and predisposition to alcohol dependence in diverse settings.

Adult↗

PubMed2002

Platelet adenylyl cyclase activity as a state or trait marker in alcohol dependence: results of the WHO/ISBRA Study on State and Trait Markers of Alcohol Use and Dependence.

BACKGROUND: There has been considerable interest in identifying biochemical markers indicative of a genetic predisposition to alcohol dependence ("trait markers"), as well as biochemical markers of recent alcohol drinking ("state markers"). Platelet adenylyl cyclase activity has been suggested as a trait and/or as a state marker related to alcohol dependence. We have now measured platelet adenylyl cyclase activity in more than 1400 well-characterized subjects, which allows us to investigate the influence of a broad range of factors on this activity. METHODS: Subjects were recruited as part of the WHO/ISBRA Study on State and Trait Markers of Alcohol Use and Dependence and were interviewed by using the WHO/ISBRA Interview Schedule. Adenylyl cyclase activity (basal, cesium fluoride [CsF]-, forskolin- and Gpp(NH)p-stimulated activities) was measured in platelet samples that were obtained at the time of interview. Data were analyzed by multivariate regression analyses. RESULTS: The multivariate analyses revealed that recent abstinence from alcohol was associated with diminutions in platelet adenylyl cyclase activities. A positive family history of alcohol dependence was associated with higher levels of adenylyl cyclase activities, and there was a significant interaction between the effect of alcohol consumption in the past month and family history of alcohol dependence; that is, the influence of alcohol consumption depended on whether the individual had a positive family history. A history of marijuana abuse also was associated with higher levels of platelet adenylyl cyclase activities, and a history of major depression was associated with lower levels of forskolin- and CsF-stimulated activities. Sex, race, and site of recruitment also affected some adenylyl cyclase activities, but there was no significant association of alcohol dependence or abuse with any of the platelet adenylyl cyclase activities. DISCUSSION: The large population and extensive characterization of subjects in this study provided an advantage over previous studies in which only the association of a few individual factors with adenylyl cyclase activity was investigated. The results demonstrate that although platelet adenylyl cyclase activity could be useful as a trait marker of alcohol dependence, its reliability in this regard is diminished by the influence of recent alcohol drinking and other variables. The associations between platelet adenylyl cyclase activities and marijuana abuse, as well as a history of depression, suggest that it may be worthwhile to study the genetic association of adenylyl cyclases (e.g., polymorphisms in the genes that code for particular adenylyl cyclase isoforms) with a predisposition to depression as well as to alcohol or marijuana abuse/dependence.

Adenylyl Cyclases↗

PubMed2002

Relationships between effects of smoking, gender, and alcohol dependence on platelet monoamine oxidase-B: activity, affinity labeling, and protein measurements.

BACKGROUND: Many studies have reported apparent associations between platelet monoamine oxidase (MAO) activity and susceptibility to alcoholism and other psychiatric conditions. Alcohol-dependent individuals generally exhibit lower platelet MAO activity compared with controls, and on this basis, platelet MAO has been proposed as a potential genetic marker for predisposition to alcoholism. However, several lines of evidence also suggest that MAO activity is reduced in both the brain and platelets of smokers. Many alcohol-dependent individuals are also tobacco users, and few studies have attempted to dissociate the effect of alcohol and tobacco use on MAO activity. METHODS: Platelet MAO-B activity in 629 subjects recruited as part of the WHO/ISBRA Study of State and Trait Markers of Alcohol Use and Dependence was assayed by using a high throughput fluorescence assay. Platelet MAO-B protein concentrations were measured by analysis of immunoblots probed with a polyclonal antibody selective for MAO. Quantitative measurements of affinity labeling of platelet MAO were made by using the selective MAO-B catalytic site antagonist [3H]Ro 19-6327. RESULTS: Multiple regression analysis revealed that subjects' gender, cigarette smoking, lifetime alcohol dependence, and recruitment site each contributed independently to the variance in platelet MAO activity levels. Female subjects had significantly higher MAO activity levels than males, whereas heavy smokers had significantly lower MAO activity levels than nonsmokers. Immunoblot measurement of platelet MAO-B protein demonstrated that females had significantly higher MAO-B protein concentrations. Platelet MAO-B protein concentrations did not differ significantly between smokers and nonsmokers but were lower in subjects with a diagnosis of lifetime alcohol dependence (DSM-IV) compared with subjects who were never alcohol dependent. Measurements of affinity labeling by [3H]Ro 19-6327 of platelet MAO correlated significantly with MAO activity levels (i.e., the lower MAO-B activity in smokers was mirrored by lower levels of [3H]Ro 19-6327 binding). CONCLUSIONS: In this international population, gender, cigarette smoking, lifetime history of alcohol dependence, and recruitment site were associated with lower platelet MAO activity levels. Differences in MAO activity associated with gender and lifetime alcohol dependence can be attributed largely to differences in MAO-B protein concentration, whereas those associated with smoking behavior may be the result of binding of an inhibitor contained in cigarette smoke to platelet MAO-B at catalytic site of MAO.

Adolescent↗

PubMed2002

Streamlining microarray technology in a prototype core laboratory.

The overall scheme of a microarray experiment is summarized in Figure 3. The real benefit of using microarrays in research is gaining knowledge from the abundant data provided from the series of related microarray experiments. The core laboratory has produced three cDNA arrays, a mouse 15K array, a human 13K array, and a human apoptosis array with 350 plus apoptotic elements. Recently, the 15K array is being used in building a database for gene expression in several areas of the mouse brain and for studying transgenic and knockout mice. The apoptosis array has been used by cancer researchers to further elucidate changes and interactions between genes leading to cell death and cancer. The UCHSC Gene Expression Array Core is supported by the National Institute on Aging and the National Cancer Institute (Bethesda, MD) to serve all academic users and has a special interest in providing a solid technological base for genomic researchers interested in alcohol and cancer research.

Animals↗