PubMed Health⌕ Search

Biomedical subjects

Johannes Müller

Publications and source records attributed to Johannes Müller.

At least 19 recordsLinked to original sources
PubMed2006

Tryptophan hydroxylase-2 gene variation influences personality traits and disorders related to emotional dysregulation.

Variation in the tryptophan hydroxylase-2 gene (TPH2) coding for the rate-limiting enzyme of serotonin (5-HT) synthesis in the brain modulates responses of limbic circuits to emotional stimuli and has been linked to a spectrum of clinical populations characterized by emotional dysregulation. Here, we tested a set of common single nucleotide polymorphisms (SNPs) in and downstream of the transcriptional control region of TPH2 for association with personality traits and with risk for personality disorders in two cohorts comprising of 336 healthy individuals and 420 patients with personality disorders. Personality dimensions were assessed by the Tridimensional Personality Questionnaire (TPQ) and the revised NEO Personality Inventory (NEO-PI-R). Personality disorders were diagnosed with the Structured Clinical Interview of DSM-IV and were allocated to clusters A, B, and C. Individual SNP and haplotype analyses revealed significant differences in genotype frequencies between controls and cluster B as well as cluster C patients, respectively. In both patient groups, we observed overrepresentation of T allele carriers of a functional polymorphism in the upstream regulatory region of TPH2 (SNP G-703T, rs4570625) which was previously shown to bias responsiveness of the amygdala, a structure critically involved in emotionality. Furthermore, significant effects of TPH2 variants on anxiety-related traits defined primarily by the TPQ Harm Avoidance were found in healthy individuals. The results link potentially functional TPH2 variants to personality traits related to emotional instability as well as to cluster B and cluster C personality disorders. These findings implicate alterations of 5-HT synthesis in emotion regulation and confirm TPH2 as a susceptibility and/or modifier gene of affective spectrum disorders.

Adolescent↗
PubMed2006

Dopamine and cognitive control: the influence of spontaneous eyeblink rate, DRD4 exon III polymorphism and gender on flexibility in set-shifting.

Converging evidence suggests a modulatory role of dopamine in cognitive control. We investigated the influence of two correlates of dopaminergic activity, the spontaneous eyeblink rate and the DRD4 exon III polymorphism, and the potential impact of gender on flexibility in an attentional set-shifting paradigm. The objective of the study was to confirm previous findings of an association between high eyeblink rates and increased cognitive flexibility. These findings were replicated in 87 healthy volunteers this time using a continuous variable for eyeblink rates instead of a dichotomized variable. The interaction between eyeblink rate and DRD4 found in the previous study was lower and failed significance. Analysis of the collapsed sample of n=150 revealed a main effect of gender and an interaction of gender and eyeblink rate on cognitive control. The complete prediction model explained 26% of the total variance. These data suggest that (1) the eyeblink rate is a reliable predictor of dopamine-mediated flexibility of cognitive control and (2) it is useful to include gender as predictor in future studies of dopaminergic modulation of cognitive control.

Adolescent↗
PubMed2006

Short-wavelength sensitive opsin (SWS1) as a new marker for vertebrate phylogenetics.

BACKGROUND: Vertebrate SWS1 visual pigments mediate visual transduction in response to light at short wavelengths. Due to their importance in vision, SWS1 genes have been isolated from a surprisingly wide range of vertebrates, including lampreys, teleosts, amphibians, reptiles, birds, and mammals. The SWS1 genes exhibit many of the characteristics of genes typically targeted for phylogenetic analyses. This study investigates both the utility of SWS1 as a marker for inferring vertebrate phylogenetic relationships, and the characteristics of the gene that contribute to its phylogenetic utility. RESULTS: Phylogenetic analyses of vertebrate SWS1 genes produced topologies that were remarkably congruent with generally accepted hypotheses of vertebrate evolution at both higher and lower taxonomic levels. The few exceptions were generally associated with areas of poor taxonomic sampling, or relationships that have been difficult to resolve using other molecular markers. The SWS1 data set was characterized by a substantial amount of among-site rate variation, and a relatively unskewed substitution rate matrix, even when the data were partitioned into different codon sites and individual taxonomic groups. Although there were nucleotide biases in some groups at third positions, these biases were not convergent across different taxonomic groups. CONCLUSION: Our results suggest that SWS1 may be a good marker for vertebrate phylogenetics due to the variable yet consistent patterns of sequence evolution exhibited across fairly wide taxonomic groups. This may result from constraints imposed by the functional role of SWS1 pigments in visual transduction.

Animals↗
PubMed2006

Determination of secondary, oxidised di-iso-nonylphthalate (DINP) metabolites in human urine representative for the exposure to commercial DINP plasticizers.

Di-iso-nonylphthalate (DINP) is the major plasticizer for polyvinylchloride (PVC) polymers. Two DINP products are currently produced: DINP 1 and DINP 2. We analyzed the isononyl alcohol mixtures (INA) used for the synthesis of these two DINP plasticizer products and thus identified 4-methyloctanol-1 as one of the major constituents of the alkyl side chains of DINP 1 (8.7%) and DINP 2 (20.7%). Based on this isomer, we postulated the major DINP metabolites renally excreted by humans: mono-(4-methyl-7-hydroxy-octyl)phthalate (7OH-MMeOP), mono-(4-methyl-7-oxo-octyl)phthalate (7oxo-MMeOP) and mono-(4-methyl-7-carboxy-heptyl)phthalate (7carboxy-MMeHP). We present a fast and reliable on-line clean-up HPLC method for the simultaneous determination of these three DINP metabolites in human urine. We used ESI-tandem mass spectrometry for detection and isotope dilution for quantification (limit of quantification 0.5microg/l). Via these three oxidised DINP isomer standards, we quantified the excretion of all oxidised DINP isomers with hydroxy (OH-MINP), oxo (oxo-MINP) and carboxy (carboxy-MINP) functional groups. With this approach, we can for the first time reliably quantify the internal burden of the general population to DINP. Mean urinary metabolite concentrations in random samples from the general German population (n=25) were 14.9microg/l OH-MINP, 8.9microg/l oxo-MINP and 16.4microg/l carboxy-MINP. Metabolites strongly correlated with each other over all samples analyzed (R>0.99, p<0.0001).

Adolescent↗
PubMed2006

Cell-cell communication by quorum sensing and dimension-reduction.

Several bacterial taxa change their behavior if the population density exceeds a certain threshold. This phenomenon is the consequence of a communication system between the bacteria and is called quorum sensing (QS). Up to now, this phenomenon is mostly modeled at population level. However, new experimental techniques allow for single cell analysis. We introduce a modeling approach for the description of this QS system, including a discussion of the regulatory network and its bistable behavior. Based on this single-cell model we develop and analyze a spatially structured model for a cell population. Special attention is given to the scaling behavior w.r.t. the cell size (leading to an approximation theorem for stationary solutions) and its consequences for the interpretation of cell communication (QS versus diffusion sensing). Concluding, we apply the modeling approach to spatially structured experimental data.

4-Butyrolactone↗
PubMed2006

Snake fangs from the Lower Miocene of Germany: evolutionary stability of perfect weapons.

There is a general consensus that most of today's nonvenomous snakes are descendants of venomous snakes that lost their venomous capabilities secondarily. This implies that the evolutionary history of venomous snakes and their venom apparatus should be older than the current evidence from the fossil record. We compared some of the oldest-known fossil snake fangs from the Lower Miocene of Germany with those of modern viperids and elapids and found their morphology to be indistinguishable from the modern forms. The primary function of recent elapid and viperid snake fangs is to facilitate the extremely rapid, stab-like application of highly toxic venoms. Our findings therefore indicate that the other components of the venom-delivery system of Early Miocene vipers and elapids were also highly developed, and that these snakes used their venom in the same way as their modern relatives. Thus, the fossil record supports the view that snakes used their venoms to rapidly subdue prey long before the mid-Tertiary onset of the global environmental changes that seem to have supported the successful radiation of venomous snakes.

Animals↗
PubMed2006

The phylogeny of early eureptiles: comparing parsimony and Bayesian approaches in the investigation of a basal fossil clade.

For the first time the phylogenetic relationships of early eureptiles, consisting of captorhinids, diapsids, and protorothyridids, are investigated in a modern phylogenetic context using both parsimony and Bayesian approaches. Ninety parsimony-informative characters and 25 taxa were included in the analyses. The Bayesian analysis was run with and without a gamma-shape parameter allowing for variable rates across characters. In addition, we ran two more Bayesian analyses that included 42 autapomorphies and thus parsimony-uninformative characters in order to test the effect of variable branch lengths. The different analyses largely converged to the same topology, suggesting that the "protorothyridid" Coelostegus is the sister taxon of all other eureptiles and that the remaining "protorothyridids" are paraphyletic. Also, there is a close relationship between diapsids and Anthracodromeus, Cephalerpeton, and Protorothyris, a grouping of Thuringothyris with captorhinids, and a variable position of the "protorothyridids" Brouffia, Hylonomus, and Paleothyris. The lack of resolution in some parts of the tree might be due to "hard polytomies" and short divergence times between the respective taxa. The tree topology is consistent with the hypothesis that the temporal fenestrations of diapsid reptiles appear to be the consequence of a more lightly built skeleton, indicating a significant ecological shift in the early stages of diapsid evolution. Bayesian analysis is a very useful additional approach in studies of fossil taxa in which more traditional statistical support like the bootstrap is often weak. However, the exclusive use of the Mk model appears suitable only if autapomorphic characters are included, whereas the Mk+gamma model performed well with or without autapomorphies.

Animals↗
PubMed2005

Four well-constrained calibration points from the vertebrate fossil record for molecular clock estimates.

Recent controversy about the use of the vertebrate fossil record for external calibration of molecular clocks centers on two issues, the number of dates used for calibration and the reliability of the fossil calibration date. Viewing matters from a palaeontological perspective, we propose three qualitative, phylogenetic criteria that can be used within a comparative framework for the selection of well-constrained calibration dates from the vertebrate fossil record. On the basis of these criteria, we identify three highly suitable new fossil calibration dates for molecular clock estimates: the lungfish-tetrapod split (between 419 and 408 Ma), the bird-crocodile split (between 251 and 243 Ma), and the alligator-caiman split (between 71 and 66 Ma). Together with our previously suggested bird-lizard split (between 252 and 257 Ma), these four fossil dates span a range of very different ages. They are, in our opinion, more suitable for molecular clock calibration than the traditionally used mammal-bird split, which is less well constrained. We plea for closer interactions between paleontologists and molecular biologists in studying the timescale of vertebrate evolution.

Animals↗
PubMed2005

Reduced oxidative stress in parallel to improved cardiac performance one year after selective removal of anti-beta 1-adrenoreceptor autoantibodies in patients with idiopathic dilated cardiomyopathy: data of a preliminary study.

Patients with idiopathic dilated cardiomyopathy (IDC) were treated with selective immunoadsorption to remove anti-beta 1-adrenoreceptor autoantibodies (anti-beta1A-AB). After one year, the effect on cardiac performance and oxidative stress was tested. Extracorporeal immunoadsorption of the whole IgG class in IDC patients for the removal of anti-beta1A-AB reduced oxidative stress in parallel to an improvement of cardiac performance. However, the non-specificity of IgG adsorption means that these beneficial effects cannot be attributed exclusively to anti-beta1A-AB removal. In an open clinical pilot study enrolling 8 patients with IDC prior to and one year after selective immunoadsorption of anti-beta1A-AB, plasma markers for oxidative stress--thiobarbituric acid-reactive substances (TBARS), lipid peroxides (LPO) and anti-oxidized low-density lipoprotein autoantibodies (anti-oxLDL-AB)--were measured in parallel to evaluation of the left ventricular function using conventional echocardiography and wall motion analysis by tissue Doppler imaging. After one year, TBARS (Wilcoxon test with bootstrapping simulation for paired data: 95% confidence interval of the P value 0.020 to 0.029) and anti-oxLDL-AB (P = 0.025 to 0.035) were decreased in parallel to an improvement of the peak systolic wall motion velocity (P = 0.006 to 0.01) and left ventricular ejection fraction (P = 0.002 to 0.02). For changes over the study period, a direct correlation with borderline significance (P = 0.076) was calculated for TBARS to the left ventricular diameter in the diastole. One year after selective immunoadsorption for anti-beta1A-AB removal, patients with ICD show a reduction in oxidative stress and a parallel improvement in cardiac performance.

Adsorption↗
PubMed2005

Successive maturation and senescence of individual leaves during barley whole plant ontogeny reveals temporal and spatial regulation of photosynthetic function in conjunction with C and N metabolism.

During ontogeny of barley plants (Hordeum vulgare, L. cv. Barke), a continuous developmental gradient of new leaves at the top and lower leaves undergoing senescence is maintained. In the course of senescence, specific recycling processes efficiently transfer valuable resources, e.g. nitrogen and carbon, to the growing young leaves and ears. In order to understand the temporal and spatial sequence of processes underlying this developmental program of leaf formation and degradation, changes in photosynthetic parameters, as well as C and N levels of all individual leaves were determined. During whole plant ontogeny, a strict sequential pattern of incorporation and degradation of C and N resources in the individual leaves, accompanied by a sequential loss of chlorophyll and photosynthetic function, was observed. In addition, protein levels of key enzymes of C and N anabolism AGPase (ADPglucose pyrophosphorylase) and GS (glutamine synthetase; plastidic isoform) also showed a strict pattern of sequential down-regulation in senescing leaves. Their decline preceded the breakdown of chlorophyll, total C and N levels and photosynthetic performance in the leaves. Quantitative real time PCR measurements revealed that the down-regulation of protein content of AGPase and GS correlated with a drastic decrease in their transcript levels. These data elucidated precise temporal and spatial regulation of C and N metabolism and allocation with photosynthetic function in the leaves during whole plant ontogeny of barley.

Base Sequence↗
PubMed2005

Dopamine and cognitive control: the influence of spontaneous eyeblink rate and dopamine gene polymorphisms on perseveration and distractibility.

One fundamental problem of intelligent organisms pursuing goal-directed behavior is how to dynamically regulate the balance between maintenance and flexibility. The authors show that central dopaminergic activity, as indicated by spontaneous eyeblink rate and dopamine gene polymorphisms, plays an important role in the modulation of this balance. Seventy-two young adults were examined. Participants with high blink rates showed increased cognitive flexibility but decreased cognitive stability compared with participants with low blink rates. This pattern of results was even more pronounced for carriers of the DRD4 exon III 4/7 genotype, even though no main effects were found for DRD4 and COMT polymorphisms. Results converge with neuropsychological models that suggest a modulatory role of prefrontal dopaminergic activity for processes of cognitive control.

Adolescent↗
PubMed2005

Cluster B personality disorders are associated with allelic variation of monoamine oxidase A activity.

Genetic variants of the monoamine oxidase A (MAOA) have been associated with aggression-, anxiety-, and addiction-related behavior in several nonclinical and clinical populations. Here, we investigated the influence of allelic variation of MAOA activity on aggression-related personality traits and disease risk in patients with personality disorders. Personality disorders were diagnosed with the Structured Clinical Interview of DSM-IV and were allocated to cluster A, B, and C. Personality features were assessed by the revised NEO Personality Inventory and the Tridimensional Personality Questionnaire. The genotype of the MAOA gene-linked polymorphic region (MAOA-LPR) was determined in 566 patients with personality disorders and in 281 healthy controls. MAOA genotype was significantly associated with cluster B personality disorders (chi2=7.77, p=0.005, df=1) but not with cluster C personality disorders. In total, 26.0% of cluster B patients were hemi- or homozygous for the low-activity variant of the MAOA genotype, compared to 16.4% in the control group. Associations between MAOA variants and personality domains related to impulsivity and aggressiveness were inconsistent. Our findings further support the notion that allelic variation of MAOA activity contributes modestly to the balance of hyper- (impulsive-aggressive) and hyporeactive (anxious-depressive) traits.

Adolescent↗
PubMed2004

Dopamine D4 receptor exon III genotype influence on the auditory evoked novelty P3.

The functional implications of the dopamine D4 receptor gene (DRD4) exon III polymorphism and its role in the modulation of temperament and in the pathophysiology of psychiatric disorders are still a matter of debate. Based on evidence from animal studies, we hypothesised that this polymorphism is involved in the modulation of the cortical response to novelty as reflected by the auditory evoked novelty P3 event-related potential. In a sample of 46 healthy volunteers, we observed an interactive effect of DRD4 exon III genotype and the eye-blink rate, a measure of central dopaminergic activity, on the novelty P3. These findings suggest that the DRD4 exon III polymorphism influences the processing of novelty and that this influence depends on tonic dopaminergic activity.

Acoustic Stimulation↗
PubMed2004

Economic evaluation and survival analysis of immunoglobulin adsorption in patients with idiopathic dilated cardiomyopathy.

Idiopathic dilated cardiomyopathy (DCM) is a life-threatening heart disease and a major reason for heart transplantations. The medical efficacy of immunoadsorption (IA) for DCM patients has been demonstrated in initial clinical studies. This prospective matched-case control study examined 5-year survival rates, direct medical costs, and cost-effectiveness in Germany (n=34) from a health-care system perspective. In a cost-effectiveness analysis costs per life year gained were calculated. Patients treated with IA showed a greater survival rate: 5-year survival rate in the intervention group was 82% vs. 41% in controls. Log rank statistics after Kaplan-Meier analysis of cumulated survival probability were highly significant. Initial intervention costs for IA were found to be 28,400 euro per patient treated. Direct medical costs for a 5-year follow-up were 128,600 euro per patient treated with IA and 75,500 euro in controls. Considering only the actual survival time we calculated annual treatment costs of 24,900 euro in the IA group and 28,900 euro in controls. The cost-effectiveness ratio expressed in costs per life year gained was 34,400 euro. This is the first controlled study to perform 5-year survival analysis and economic evaluation of this new emerging technology for patients with DCM. Although high initial treatment costs for IA are incurred, the significantly better survival rates lead to reasonable costs per live year gained.

Adsorption↗
PubMed2004

First experiences with a novel magnetically suspended axial flow left ventricular assist device.

UNLABELLED: Axial flow pumps have gained increased acceptance since their first clinical use in 1998. The present report summarizes the clinical experience with patients treated for severe cardiogenic shock for the first time with a newly developed axial flow pump with magnetically levitated bearings. MATERIAL AND METHODS: The axial flow pump Incor was implanted in 24 patients between June 2002 and June 2003. All except one patient were men. In 16 patients dilative cardiomyopathy, in seven ischemic and in one restrictive cardiomypathy had been diagnosed. All patients presented with catecholamine-dependent end-stage heart failure, seven of them were on an artificial ventilator and three were dependent on intraaortic balloon pump support. All patients suffered from organ dysfunction resulting from low cardiac output. RESULTS: There were no perioperative deaths. The 30-day mortality rate was 8% (n = 2); 79% ( n = 19) of patients reached a condition to be discharged home. The cumulative time on the device is 6.9 years; the longest individual time up to July 1, 2003 is 12.6 months. There were no structural defects or failures of the system. In one case the controller had to be exchanged because of intermittent malfunction. Cardiac output ranged between 4 and 6 l in all instances and there were no cases of infection of the drive-line or the system. Hemolysis was present initially but was not detectable in the later course. There were three instances of transient ischemic attacks. Two patients developed late cardiac tamponade with re-opening of the chest after 9 and 14 days. In one patient persistent gastrointestinal bleeding required re-hospitalization and transfusion therapy. Two patients were weaned from the device after 6 and 7 months of support, respectively. CONCLUSION: The preliminary clinical experience with Incor is promising. The flow is sufficient for recovery from multiorgan failure and the pump allows long-term hemolysis-free support. The concept of magnetically levitated bearings has proven to be durable and reliable. In the case that the heart may recover through unloading, weaning from the pump is possible.

Adult↗
PubMed2004

Non-specific removal of antibodies in patients with idiopathic dilated cardiomyopathy: implications for xenotransplantation.

We assessed the efficiency of non-specific extracorporeal immunoadsorption (EIA), using polyclonal anti-human immunoglobulin antibodies, in depleting the serum of anti-galactosealpha1,3galactose (Gal) antibody and in decreasing serum cytotoxicity in 5 patients with idiopathic dilated cardiomyopathy. The mean concentrations of anti-Gal immunoglobulin (Ig)M and IgG before EIA were 74 microg/ml and 159 microg/ml, respectively. After EIA, these concentrations decreased by 86% and 88%, respectively. Both anti-Gal IgM and IgG returned to pre-EIA concentrations within 1 month, without rebound to greater than baseline concentrations. After EIA, mean serum cytotoxicity also decreased from 90% to 17%, with recovery by 1 month. Extracorporeal immunoadsorption proved safe in patients with heart failure and was effective in depleting anti-Gal antibody and in decreasing serum cytotoxicity to pig cells.

Adult↗