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Biomedical subjects

G Dietz

Publications and source records attributed to G Dietz.

At least 19 recordsLinked to original sources
PubMed2003

[Absorption of L-lysine diatrizoate from the gastrointestinal tract: the influence of surgery, inflammation and neoplasia].

PURPOSE: To ascertain whether the absorption of L-lysine diatrizoate, a sodium-free salt of the contrast-giving diatrizoic acid, from the gastrointestinal tract is increased by surgery, inflammation or neoplasia. MATERIAL AND METHODS: Using contrast medium containing L-lysine diatrizoate for intestinal opacification, this prospective study compared 32 radiographic examinations of the upper gastrointestinal tract with 52 radiographic examination of the lower gastrointestinal tract. In blood samples taken from the patients immediately after the radiographic examinations, the concentration of diatrizoic acid was determined by high pressure liquid chromatography. The results were correlated with sex, age, surgical history and any evidence of inflammatory or neoplastic diseases. RESULTS: The serum diatrizoic acid concentration in patients after oral administration was 3.62 (95% CI, 2.86 - 10.17) microg/ml. The titer was lower in patients who had undergone abdominal surgery than in patients without surgery. Serum diatrizoic acid concentration in patients after rectal administration was 0.30 (95% CI, 0.13 - 0.60) microg/ml. The titer was significantly higher (p < 0.05) in patients suffering from inflammatory conditions or neoplasms than in the other patients. CONCLUSION: The L-lysine salt of diatrizoic acid is absorbed in larger amounts from the upper than from the lower gastrointestinal tract. Absorption is not increased after abdominal surgery. However, inflammatory conditions and neoplasms of the large bowel increase the uptake of contrast medium from the intestine.

Abdomen↗
PubMed2001

The additive effect of neurotransmitter genes in pathological gambling.

As access to gambling increases there is a corresponding increase in the frequency of addiction to gambling, known as pathological gambling. Studies have shown that a number of different neurotransmitters are affected in pathological gamblers and that genetic factors play a role. Polymorphisms at 31 different genes involved in dopamine, serotonin, norepinephrine, GABA and neurotransmitters were genotyped in 139 pathological gamblers and 139 age, race, and sex-matched controls. Multivariate regression analysis was used with the presence or absence of pathological gambling as the dependent variable, and the 31 coded genes as the independent variables. Fifteen genes were included in the regression equation. The most significant were the DRD2, DRD4, DAT1, TPH, ADRA2C, NMDA1, and PS1 genes. The r(2) or fraction of the variance was less than 0.02 for most genes. Dopamine, serotonin, and norepinephrine genes contributed approximately equally to the risk for pathological gambling. These results indicate that genes influencing a range of brain functions play an additive role as risk factors for pathological gambling. Multi-gene profiles in specific individuals may be of assistance in choosing the appropriate treatment.

Adult↗
PubMed2000

Comparison of the role of dopamine, serotonin, and noradrenaline genes in ADHD, ODD and conduct disorder: multivariate regression analysis of 20 genes.

The present study is based on the proposal that complex disorders resulting from the effects of multiple genes are best investigated by simultaneously examining multiple candidate genes in the same group of subjects. We have examined the effect of 20 genes for dopamine, serotonin, and noradrenergic metabolism on a quantitative score for attention deficit hyperactivity disorder (ADHD) in 336 unrelated Caucasian subjects. The genotypes of each gene were assigned a score from 0 to 2, based on results from the literature or studies in an independent set of subjects (literature-based scoring), or results based on analysis of variance for the sample (optimized gene scoring). Multivariate linear regression analysis with backward elimination was used to determine which genes contributed most to the phenotype for both coding methods. For optimized gene scoring, three dopamine genes contributed to 2.3% of the variance, p = 0.052; three serotonin genes contributed to 3%, p = 0.015; and six adrenergic genes contributed to 6.9%, p = 0.0006. For all genes combined, 12 genes contributed to 11.6% of the variance, p = 0.0001. These results indicate that the adrenergic genes play a greater role in ADHD than either the dopaminergic or serotonergic genes combined. The results using literature-based gene scoring were similar. An examination of two additional comorbid phenotypes, conduct disorder and oppositional defiant disorder (ODD), indicated they shared genes with ADHD. For ODD different genotypes of the same genes were often used. These results support the value of the simultaneous examination of multiple candidate genes.

Adolescent↗
PubMed2000

Multivariate analysis of associations of 42 genes in ADHD, ODD and conduct disorder.

In a previous study (Comings DE et al. Comparison of the role of dopamine, serotonin, and noradrenergic genes in ADHD, ODD and conduct disorder. Multivariate regression analysis of 20 genes. Clin Genet 2000: 57: 178-196) we examined the role of 20 dopamine, serotonin and norepinephrine genes in attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), and conduct disorder (CD), using a multivariate analysis of associations (MAA) technique. We have now brought the total number of genes examined to 42 by adding an additional 22 candidate genes. These results indicate that even with the inclusion of these additional genes the noradrenergic genes still played a greater role in ADHD than any other group. Six other neurotransmitter genes were included in the regression equation - cholinergic, nicotinic, alpha 4 receptor (CHNRA4), adenosine A2A receptor (ADOA2A), nitric oxide synthase (NOS3), NMDAR1, GRIN2B, and GABRB3. In contrast to ADHD and ODD, CD preferentially utilized hormone and neuropeptide genes These included CCK, CYP19 (aromatase cytochrome P-450), ESR1, and INS (p = 0.005). This is consistent with our prior studies indicating a role of the androgen receptor (AR) gene in a range of externalizing behavors. We propose that the MAA technique, by focusing on the additive effect of multiple genes and on the cummulative effect of functionally related groups of genes, provides a powerful approach to the dissection of the genetic basis of polygenic disorders.

Adolescent↗
PubMed2000

A multivariate analysis of 59 candidate genes in personality traits: the temperament and character inventory.

Cloninger (Cloninger CR. Neurogenetic adaptive mechanisms in alcoholism. Science 1987: 236: 410-416) proposed three basic personality dimensions for temperament: novelty seeking, harm avoidance, and reward dependence. He suggested that novelty seeking primarily utilized dopamine pathways, harm avoidance utilized serotonin pathways, and reward dependence utilized norepinephrine pathways. Subsequently, one additional temperament dimension (persistence) and three character dimensions (cooperativeness, self-directedness, and self-transcendence) were added to form the temperament and character inventory (TCI). We have utilized a previously described multivariate analysis technique (Comings DE, Gade-Andavolu R, Gonzalez N et al. Comparison of the role of dopamine, serotonin, and noradrenergic genes in ADHD, ODD and conduct disorder. Multivariate regression analysis of 20 genes. Clin Genet 2000: 57: 178-196; Comings DD, Gade-Andavolu R, Gonzalez N et al. Multivariate analysis of associations of 42 genes in ADHD, ODD and conduct disorder. Clin Genet 2000: in press) to examine the relative role of 59 candidate genes in the seven TCI traits and test the hypothesis that specific personality traits were associated with specific genes. While there was some tendency for this to be true, a more important trend was the involvement of different ratios of functionally related groups of genes, and of different genotypes of the same genes, for different traits.

Adult↗
PubMed2000

Association of the neutral endopeptidase (MME) gene with anxiety.

Enkephalins have been implicated in the regulation of mood, anxiety, reward, euphoria and pain. One of the major enzymes for enkephalin degradation is neutral endopeptidase [enkephalinase, membrane metalloendopeptidase (MME)]. We identified a dinucleotide polymorphism in the 5' region of the MME gene. Subjects were placed into three genotypes, 3/3, 3/x, and x/x since the 3 allele was the most common of the six alleles. Using one-way analysis of variance, we examined the association of these genotypes with the mean SCL-90 scores for anxiety, depression, obsessive-compulsive and phobic anxiety symptoms in 120 Caucasian males from an addiction treatment unit. There was a significant association between the MME genotypes and the SCL-90 scores for phobic anxiety, obsessive-compulsive and anxiety at a Bonferroni corrected alpha value of 0.0125. These results support a role of genetic variants of enkephalin metabolism in anxiety.

Adult↗
PubMed1999

Association of the enkephalinase gene with low amplitude P300 waves.

Low amplitude of the P300 evoked potential waves has been linked to substance abuse. Defects in opioidergic genes regulating reward pathways have been implicated as risk factors in substance abuse. Since the rate of degradation of enkephalins regulates their CNS level, we focused on the MME gene for metallo-membrane endopeptidase (neutral endopeptidase, enkephalinase). We identified a GT repeat polymorphism 5' to the gene and examined its potential association with P300 wave amplitude in 25 male subjects with substance abuse. There was significant association of low mol. wt alleles with low amplitude of the P300 wave at the parietal (p = 0.0087) and coronal (p = 0.009) leads. These results support a role of endogenous opioids in the regulation of P300 wave amplitude.

Acoustic Stimulation↗
PubMed1999

The proenkephalin gene (PENK) and opioid dependence.

We tested the hypothesis that the alleles at the (CA)n repeat of the proenkephalin gene (PENK) might be associated with opioid addiction in 31 non-Hispanic Caucasian subjects with opioid dependence (heroin), 89 ethnically matched subjects with substance dependence other than opioid dependence and 132 controls. Among the subjects with opioid dependence, 66% carried the > or = 81 bp allele compared with 40% of subjects with other types of substance abuse (chi2 = 11.31, p < 0.004) and 49% of controls (chi2 = 6.0, p < 0.015). These results are consistent with a role of the PENK gene in opioid dependence.

Adult↗
PubMed1998

Supernatant from stored red cells activates neutrophils.

Bioreactive substances including cytokines and lipids accumulate during storage of red blood cells (RBCs) but their clinical importance is uncertain. The goal of this study was to evaluate the effect of stored RBC supernatant on neutrophil activity in vitro. Packed RBCs (PRBCs) were collected and divided into two aliguots, one leukodepleted and the other nonleukodepleted. Plasma supernatant from PRBCs were collected on days 1, 8, 15, 29 and 35 and its effect on neutrophil expression of CD11b, CD16 and oxidative burst was measured by flow cytometry. Levels of tumour necrosis factor alpha (TNF alpha) and interleukin-8 (IL8) were also measured. The supernatant from PRBC units stored for greater than 15 days activated and primed neutrophils as evidenced by an increase CD11b and CD16 expression and oxidative burst. The greatest effect was seen in the oldest concentrates (35-day-old) (P < 0.008). Leukodepletion abrogated the effects of stored supernatant on CD11b and CD16 expression (P < 0.02) but did not reduce priming of the neutrophil oxidative burst (P > 0.1). Very low levels of IL8 and TNF alpha were detected in stored supernatants. Stored PRBC supernatant contains substances which directly enhance neutrophil expression of adhesion protein CD11b, CD16 and prime neutrophil oxidative burst. The exceedingly low level of IL8 and TNF alpha found in this study suggests that other factors may play a more important role in neutrophil priming and activation.

Biomarkers↗
PubMed1997

Studies of the potential role of the dopamine D1 receptor gene in addictive behaviors.

Abnormalities in the dopaminergic reward pathways have frequently been implicated in substance abuse and addictive behaviors. Recent studies by Self and coworkers have suggested an important interaction between the dopamine D1 and D2 receptors in cocaine abuse. To test the hypothesis that the DRD1 gene might play a role in addictive behaviors we examined the alleles of the Dde I polymorphism in three independent groups of subjects with varying types of compulsive, addictive behaviors-Tourette syndrome probands, smokers and pathological gamblers. In all three groups there was a significant in the frequency of homozygosity for the DRD1 Dde I 1 or 2 alleles in subjects with addictive behaviors. The DRD1 11 or 22 genotype was present in 41.3% of 63 controls and 57.3% of 227 TS probands (P = 0.024). When 23 quantitative traits were examined by ANOVA those carrying the 11 genotype consistently had the highest scores. Based on these results, we examined the prevalence of the 11 genotype in controls, TS probands without a specific behavior, and TS probands with a specific behavior. There was a progressive, linear increase, significant at alpha < or = 0.005 for scores for gambling, alcohol use and compulsive shopping. Problems with three additional behaviors, drug use, compulsive eating and smoking were significant at alpha < or = 0.05. All six variables were related to addictive behaviors. In a totally separate group of controls and individuals attending a smoking cessation clinic, and smoking at least one pack per day, 39.3% of the controls versus 66.1% of the smokers carried the 11 or 22 genotype (P = 0.0002). In a third independent group of pathological gamblers, 55.8% carried the 11 or 22 genotype (P = 0.009 vs the combined controls). In the TS group and smokers there was a significant additive effect of the DRD1 and DRD2 genes. The results for both the DRD1 and DRD2 genes, which have opposing effects on cyclic AMP, were consistent with negative and positive heterosis, respectively. These results support a role for genetic variants of the DRD1 gene in some addictive behaviors, and an interaction of genetic variants at the DRD1 and DRD2 genes.

Adult↗
PubMed1996

Polygenic inheritance of Tourette syndrome, stuttering, attention deficit hyperactivity, conduct, and oppositional defiant disorder: the additive and subtractive effect of the three dopaminergic genes--DRD2, D beta H, and DAT1.

Polymorphisms of three different dopaminergic genes, dopamine D2 receptor (DRD2), dopamine beta-hydroxylase (D beta H), and dopamine transporter (DAT1), were examined in Tourette syndrome (TS) probands, their relatives, and controls. Each gene individually showed a significant correlation with various behavioral variables in these subjects. The additive and substractive effects of the three genes were examined by genotyping all three genes in the same set of subjects. For 9 of 20 TS associated comorbid behaviors there was a significant linear association between the degree of loading for markers of three genes and the mean behavior scores. The behavior variables showing the significant associations were, in order attention deficit hyperactivity disorder (ADHD), stuttering oppositional defiant, tics, conduct, obsessive-compulsive, mania, alcohol abuse and general anxiety-behaviors that constitute the most overt clinical aspects of TS. For 16 of the 20 behavior scores there was a linear progressive decrease in the mean score with progressively lesser loading for the three gene markers. These results suggest that TS, ADHD, stuttering oppositional defiant and conduct disorder, and other behaviors associated with TS, are polygenic, due in part to these three dopaminergic genes, and that the genetics of other polygenic psychiatric disorders may be deciphered using this technique.

Adolescent↗
PubMed1996

A study of the dopamine D2 receptor gene in pathological gambling.

Pathological gambling has been termed both the 'pure' and the 'hidden' addiction. 'Pure' because it is not associated with the intake of any addicting substance, and 'hidden' because it is an extension of a common, socially accepted behaviour. The Taq A1 variant of the human DRD2 gene has been associated with drug addiction, some forms of severe alcoholism, and other impulsive, addictive behaviours. We have sought to determine if there is a similar association with pathological gambling. A total of 222 non-Hispanic Caucasian pathological gamblers from multiple sites across the US participated in the study. Of these 171 donated a sample of blood, 127 filled out several questionnaires, and 102 did both. Of the 171 pathological gamblers 50.9% carried the D2A1 allele versus 25.9% of the 714 known non-Hispanic Caucasian controls screened to exclude drug and alcohol abuse, p < 0.00000001, odds ratio (OR) = 2.96. For the 102 gamblers who filled out the questionnaires, 63.8% of those in the upper half of the Pathological Gambling Score (more severe) carried the D2A1 allele (OR versus controls = 5.03), compared to 40.9% in the lower half (less severe). Of those who had no comorbid substance abuse, 44.1% carried the D2A1 allele, compared to 60.5% of those who had comorbid substance abuse. Forty-eight controls and 102 gamblers completed a shorter version of the Pathological Gambling Score. Of the 45 controls with a score of zero, 17.8% carried the D2A1 allele. Of the 99 gamblers with a score of 5 or more, 52.5% carried the D2A1 allele (chi 2 = 15.36, p = 0.00009). These results suggest that genetic variants at the DRD2 gene play a role in pathological gambling, and support the concept that variants of this gene are a risk factor for impulsive and addictive behaviours.

Adult↗
PubMed1996

Exon and intron variants in the human tryptophan 2,3-dioxygenase gene: potential association with Tourette syndrome, substance abuse and other disorders.

Defects in serotonin metabolism, and abnormalities in both blood serotonin and tryptophan levels, have been reported in many psychiatric disorders. Tryptophan 2,3-dioxygenase (TDO2) is the rate limiting enzyme for the breakdown of tryptophan to N-formyl kenurenine. Functional variants of this gene could account for the observed simultaneous increases or decreases of both serotonin and tryptophan in various disorders. We have identified four different polymorphisms of the human TDO2 gene. Association studies show a significant association of one or more of these polymorphisms and Tourette syndrome (TS), attention deficit hyperactivity disorder (ADHD) and drug dependence. The intron 6G-->T variant was significantly associated with platelet serotonin levels. Only the association with TS was significant with a Bonferroni correction (p = 0.005). Our purpose here is not to claim these associations are proven, but rather to report preliminary results and show that easily testable polymorphisms are available. We hope to encourage additional research into the potential role the TDO2 gene in these and other psychiatric disorders.

Electrophoresis, Polyacrylamide Gel↗
PubMed1996

[Multiparity in Nicaragua].

The relation between birthweight and parity of the mother was examined in Nicaraguan patients from the capital Managua. 7431 births were taken into consideration from 1989-1991. 564 (= 7.6%) of these newborns were born to mothers with more than 5 deliveries. A positive correlation between the increasing number of the parity and the birthweight can be demonstrated in our patients until parity 10, however there are decreases in the birthweight of female newborns between parity 3 to 4 and 5 to 6 and in males between parity 6 to 7 and parity 8 to 9. The average age of a Nicaraguan primipara is 20.7 years and increases by 1.9-2.4 years until parity 5. From parity 6 to parity 15 it increases only by 0.7-1.2 years.

Adult↗
PubMed1995

Sequence of human tryptophan 2,3-dioxygenase (TDO2): presence of a glucocorticoid response-like element composed of a GTT repeat and an intronic CCCCT repeat.

Abnormalities in serotonin levels have been implicated in a wide range of psychiatric disorders. Tryptophan 2,3-dioxygenase is the rate-limiting enzyme in the catabolism of tryptophan, the precursor of serotonin. As such it is a potential major candidate gene in psychiatric genetics. The regulatory, intron, and exon regions of the human TDO2 gene have been sequenced. Twelve exons were identified. The amino acid sequence of the enzyme was 88% homologous to that of the rat. Compared to the rat, the regulatory region of the human TDO2 gene had an insertion of approximately 1064 bp of random DNA beginning at -293 bp and extending to -1357 bp. This displaced the glucocorticoid response element (GRE) occurring at -1174 bp in the rat to -1500 in the human. The proximal GRE at -419 in the rat was missing in the human. However, within the DNA insert there was a GRE-like microsatellite region containing multiple GTT repeats plus additional GT(n) sequences. This could produce several staggered regions of the sequence TGTTGTnnnTGTTGT similar to a GRE consensus sequence of TGTTCAnnnTGTTCT. The intron regions 5' and 3' to each exon were sequenced This showed a HIS --> Val mutation polymorphism in exon 7. Three introns, 1,5, and 6, were completely sequenced and examined for polymorphism. This identified two polymorphisms consisting of G -- >T and G --> A mutations 2 bp apart in intron 6. The 3' end of intron 5 showed an extensive CCCT pentanucleotide repeat that was markedly polymorphic. These polymorphisms allow the TDO2 gene to be examined for a possible role in psychiatric disorders.

Amino Acid Sequence↗
PubMed1995

Dopamine D2 receptor gene (DRD2) haplotypes and the defense style questionnaire in substance abuse, Tourette syndrome, and controls.

The defence style questionnaire (DSQ) was administered to Caucasian males consisting of 123 subjects from a V.A. addiction treatment unit (ATU), 42 Tourette syndrome (TS) subjects, and 49 controls. For the ATU and TS subjects, there was a significant decrease in the mean score for mature defenses and a significant increase in mean score for immature defenses compared to controls. Many of the individual subscores showed the same significant differences. Dopamine D2 receptor (DRD2) gene haplotypes, identified by allele specific polymerase chain reaction of two mutations (G/T and C/T) 241 base pairs apart, were determined in 57 of the ATU subjects and 42 of the controls. Subjects with the 1 haplotype tended to show a decrease in mature and an increase in neurotic and immature defense styles compared to those without the 1 haplotype. Of the eight times that the subscale scores were significant for haplotype 1 versus non-1, they were always in this direction. There results suggest that the DRD2 locus is one factors controlling defense styles. The difference in the mean scores between controls and substance abuse subjects indicates that other genes and environmental factors also play a role.

Alcoholism↗