JOHN VUCHETICH - Academia.edu (original) (raw)

Papers by JOHN VUCHETICH

Genetic Epidemiology, 1995

Thiopurine methyltransferase (TPMT) catalyzes thiopurine S-methylation, an important metabolic pa... more Thiopurine methyltransferase (TPMT) catalyzes thiopurine S-methylation, an important metabolic pathway for drugs such as 6-mercaptopurine (6-MP). Inherited differences in the activity of this enzyme are related to individual differences in the therapeutic efficacy and toxicity of 6-MP and other thiopurine drugs. Variation of TPMT activity in the red blood cell (RBC) has been found to reflect activity differences in less accessible tissues. Previously reported qualitative analyses of inheritance of RBC TPMT in families suggested that a major gene plays a role in the regulation of activity of this enzyme. In the present study we completed complex segregation analyses of RBC TPMT activity of 2 13 individuals in 49 families that were randomly ascertained through children in the Rochester, MN, public school system. We found clear evidence of a major gene effect on RBC TPMT activity. Both transformed and untransformed data supported the segregation of a Mendelian major gene with frequency of 0.94 for the allele conferring high enzyme activity. The genotype distributions of individuals who were homozygous for the low activity allele, heterozygous, and homozygous for the high activity allele accounted for approximately 0.3%, 1 1.2%, and 88.5%, respectively, of the individuals in the sample. This major locus accounted for 66% of the total variance in untransformed RBC TPMT activity. Although there were significant residual family correlations among probable high activity homozygotes, there was insufficient power to detect additional major locus or polygenic inheritance effects on the residual variance.

Schizophrenia Research, Oct 1, 2010

Genetic Epidemiology, 1991

Although the structural gene for human dopamine‐β‐hydroxylase (DBH) has been cloned, the mechanis... more Although the structural gene for human dopamine‐β‐hydroxylase (DBH) has been cloned, the mechanism by which DBH physical properties and activity are regulated is not well understood. Previous reports have suggested that three‐allele or two‐locus models may account for the genetic regulation of these traits in human blood. It is an interesting challenge to determine the extent to which quantitative analyses will complement or guide molecular genetic studies. In this study we analyzed data on the physical property of DBH thermal stability and DBH activity in 230 individuals in 53 families in an attempt to clarify genetic mechanisms for the inheritance of these traits. Commingling and segregation analyses of the thermal stability data provided the first clear evidence of a major gene polymorphism for DBH thermal stability analyzed as a quantitative trait. Major gene transmission was supported within a mixed model (χ = 13.39, P < .004). In keeping with earlier findings, similar analyses of DBH activity provided strong evidence of genetic transmission. However, in our data support for a major gene polymorphism was equivocal (χ = 2.99, P = .22).

Psychiatry Research-neuroimaging, Jul 1, 2008

Efforts to determine the etiologies of mood disorders have been hampered by heterogeneity of grou... more Efforts to determine the etiologies of mood disorders have been hampered by heterogeneity of groups and failures to replicate findings. One strategy for overcoming these difficulties is to subtype disorders based on observable features in order to obtain more homogeneous groups. The groups obtained by such procedures can then be studied to determine if they comprise valid subtypes with distinct characteristics and etiologies. The current study examined 100 individuals from 21 multiplex families selected through a proband with mood disorder, as well as 25 control subjects free of Axis I mental disorder. The probands in the main family groups had all met diagnostic criteria for a highly genetic subtype of mood disorder; either rapid cycling bipolar disorder or recurrent unipolar depression. The patterns of psychopathology and normal personality variation were studied in the families of these probands. These data were used to test hypotheses predicting how the family groups would differ from each other and from normal controls. Results confirm that subtypes of mood disorder tend to run true but are also associated with increased familial risk for panic and substance use disorders. Family members of probands had increased levels of Axis II pathology: relatives of patients with recurrent unipolar depression most clearly showed increased levels of Cluster B problems, especially borderline traits, while relatives of rapid cycling bipolar patients had increased levels of obsessive-compulsive traits. Family members of probands with mood disorder also differed from controls in their pattern of scores on a measure of normal personality variation. Both groups of family members showed an elevation on the Negative Emotionality factor. However, the specific pattern of personality traits which deviated from control scores differed slightly between the two family groups. The significant differences from normal controls seen in the two groups of family members on measures of personality disorder and normal personality held even when considering only those family members who had never had a mood disorder. Study results were consistent with distinct familial subtypes of mood disorder

Human Molecular Genetics, 1992

Psychological Reports, Aug 1, 1997

Summay.-To test the hypothesis that nosologies are biased towards recognizing highly distinctive ... more Summay.-To test the hypothesis that nosologies are biased towards recognizing highly distinctive syndromes and therefore connate those that are less distinctive, eight subjects judged the distinctiveness of 33 DSM-IV disorders and 20 rheumatic disorders. As predtcted, judged distinctiveness was negatively correlated with prevalence for both sets of disorders.

Schizophrenia Research, Sep 1, 2010

High nailfold plexus visibility (NPV) is a trait identifying a putative endophenotype for schizop... more High nailfold plexus visibility (NPV) is a trait identifying a putative endophenotype for schizophrenia. We describe a new method of NPV assessment using computer storage of digital photomicrographs. We performed a reliability study of this method using 40 subjects. The intraclass correlation between two blinded raters was 0.83. The kappa coefficient for a 3 level division of NPV was 0.72, while the kappa for reliability at the cutting score for designating high NPV was 0.94. This method provides immediate image quality feedback, ease of reliability assessment, the option of blinded ratings, and a method for continuous enhancement of rating consensus.

Drug and Alcohol Dependence, 2020

Background: Smokers are often advised to use nicotine lozenge after cravings or withdrawal sympto... more Background: Smokers are often advised to use nicotine lozenge after cravings or withdrawal symptoms are present, which may be too late to prevent lapses. This study assesses if lozenge use prior to smoking cue exposure attenuates cue-induced increases in symptom severity. Methods: In this randomized, cross-over study, participants completed three laboratory sessions at which they proceeded through 4 "rooms" in a virtual reality environment. The first and last "rooms" contained neutral cues and the others contained smoking cues. At one session, a 4 mg nicotine lozenge was not given until after cue exposure (to approximate current use: i.e., after craving and withdrawal symptoms occur). At the other two sessions either a nicotine or placebo lozenge was used 15 minutes before cue exposure procedures. Craving and withdrawal symptoms were measured throughout each laboratory session. Results: Of 58 participants randomized; 40 completed all 3 labs. Absolute levels of craving and withdrawal symptom severity during cue exposure were lower when placebo or active lozenge was used prior to cue presentation procedures vs. no treatment until after cue presentation procedures (all p-values <0.05). There were no differences among conditions in the magnitude of symptom severity increase occurring between the first neutral room and the cue rooms.

Addictive Behaviors, Aug 1, 2017

Introduction-Smokers are often told to use nicotine lozenge when craving or withdrawal symptoms o... more Introduction-Smokers are often told to use nicotine lozenge when craving or withdrawal symptoms occur. This may be too late to prevent lapses. This study assessed if nicotine lozenge use prior to a common smoking trigger can minimize trigger induced increases in craving and withdrawal symptoms. Methods-Eighty-four smokers completed two laboratory sessions in random order. At one session, nicotine lozenge was given immediately after a stressor (to approximate current recommended use-i.e., after craving and withdrawal symptoms occur); at the other session subjects were randomized to receive nicotine lozenge at time points ranging from immediately to 30 minutes prior to the stressor. Withdrawal symptoms and urge to smoke were measured using the Minnesota Nicotine Withdrawal Scale and the Questionnaire of Smoking Urges (QSU). Results-Relative to receiving lozenge after the stressor, a smaller increase in pre-stressor to post-stressor withdrawal symptom scores occurred when lozenge was used immediately prior (p=0.03) and 10 minutes prior (p=0.

Springer eBooks, 2013

Behavioral medicine research is increasingly being influenced by theoretical models that explain ... more Behavioral medicine research is increasingly being influenced by theoretical models that explain individual differences in behavior and disease risk as a function of interrelated biological, behavioral, social, and contextual forces. This multi-level theoretical approach follows technical innovations that have made measuring the activity of many biological systems straightforward, portable, and cost efficient. Saliva, in particular, has received attention as a biospecimen; sample collection is perceived as feasible, cost-efficient, and safe, and salivary assays as reliable and accurate (see Table 1). A single oral fluid specimen can provide information about a range of physiologic systems, chemical exposures, and genetic variability relevant to basic biological function, health, and disease. The purpose of this review is to provide a road map for investigators interested in integrating this unique biospecimen into the next generation of studies in behavioral medicine. Description Oral fluid as a biospecimen: "Saliva" is a composite of oral fluids secreted from many different glands. The source glands are located in the upper posterior area of the oral cavity (parotid gland area), lower area of the mouth between the cheek and jaw (submandibular gland area), and under the tongue (sublingual gland area). There are also Author Notes In the interest of full disclosure, DAG is founder and Chief Strategy and Scientific Advisor at Salimetrics LLC (State College, PA). DAG's relationship with Salimetrics LLC is managed by the policies of the Conflict of Interest Committee at the

Addictive behaviors, Jan 10, 2017

Smokers are often advised to use nicotine lozenge when craving or withdrawal symptoms occur. This... more Smokers are often advised to use nicotine lozenge when craving or withdrawal symptoms occur. This may be too late to prevent lapses. This study assessed if nicotine lozenge use prior to a common smoking trigger can minimize trigger induced increases in craving and withdrawal symptoms. Eighty-four smokers completed two laboratory sessions in random order. At one session, nicotine lozenge was given immediately after a stressor (to approximate current recommended use - i.e., after craving and withdrawal symptoms occur); at the other session subjects were randomized to receive nicotine lozenge at time points ranging from immediately to 30min prior to the stressor. Withdrawal symptoms and urge to smoke were measured using the Minnesota Nicotine Withdrawal Scale and the Questionnaire of Smoking Urges (QSU). Relative to receiving lozenge after the stressor, a smaller increase in pre-stressor to post-stressor withdrawal symptom scores occurred when lozenge was used immediately (p=0.03) and ...

Psychopharmacology, 1987

This study investigated pharmacological manipulations of the cholinergic (ACh) and dopaminergic (... more This study investigated pharmacological manipulations of the cholinergic (ACh) and dopaminergic (DA) transmitter systems in monkeys with a long-term lead-induced cognitive deficit on delayed spatial alternation (DSA). Both ACh and DA have been found to be affected by developmental lead exposure and to be involved with performance on spatial learning and memory tasks. The lead-induced deficit in performance accuracy on DSA persisted throughout the 2 years of this experiment, which ended more than 8 years after the end of the postnatal lead exposure. Acute administration of agonists and antagonists of the ACh and DA systems did not elicit differential effects from the lead-exposed and control groups in terms of DSA per cent correct performance. The ACh antagonist, scopolamine, caused a dose-related decline in performance in both groups. Significant amelioration of the lead-induced DSA deficit was achieved by chronic treatment with the DA agonist, L-dopa. After withdrawal from L-dopa, the lead-related deficit reappeared. Improvement in performance of the lead-treated group was also seen after chronic amphetamine administration, but this effect was not significant. These data implicate DA mechanisms in the long-lasting cognitive effects of developmental lead exposure. The alleviation of the deficit with chronic administration of a DA precursor points to a possible line of treatment for the cognitive effects of developmental lead exposure.

Encyclopedia of Behavioral Medicine, 2013

Schizophrenia Research, 2010