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K Fuchs

Publications and source records attributed to K Fuchs.

At least 37 records · Page 2Linked to original sources
PubMed2001

Organization and neurochemistry of vagal preganglionic neurons innervating the lower esophageal sphincter in ferrets.

The motor control of the lower esophageal sphincter (LES) is critical for normal swallowing and emesis, as well as for the prevention of gastroesophageal reflux. However, there are surprisingly few data on the central organization and neurochemistry of LES-projecting preganglionic neurons. There are no such data in ferrets, which are increasingly being used to study LES relaxation. Therefore, we determined the location of preganglionic neurons innervating the ferret LES, with special attention to their relationship with gastric fundus-projecting neurons. The neurochemistry of LES-projecting neurons was also investigated using two markers of "nontraditional" neurotransmitters in vagal preganglionic neurons, nitric oxide synthase (NOS), and dopamine (tyrosine hydroxylase: TH). Injection of cholera toxin B subunit (CTB)-horseradish peroxidase (HRP) into the muscular wall of the LES-labeled profiles throughout the rostrocaudal extent of the dorsal motor nucleus of the vagus (DMN) The relative numbers of profiles in three regions of the DMN from caudal to rostral are, 43 +/- 5, 67 +/- 11, and 113 +/- 30). A similar rostrocaudal distribution occurred after injection into the gastric fundus. When CTB conjugated with different fluorescent tags was injected into the LES and fundus both labels were noted in 56 +/- 3% of LES-labeled profiles overall. This finding suggests an extensive coinnervation of both regions by vagal motor neurons. There were significantly fewer LES-labeled profiles that innervated the antrum (16 +/- 9%). In the rostral DMN, 15 +/- 4% of LES-projecting neurons also contained NADPH-diaphorase activity; however, TH immunoreactivity was never identified in LES-projecting neurons. This finding suggests that NO, but not catecholamine (probably dopamine), is synthesized by a population of LES-projecting neurons. We conclude that there are striking similarities between LES- and fundic-projecting preganglionic neurons in terms of their organization in the DMN, presence of NOS activity and absence of TH immunoreactivity. Coinnervation of the LES and gastric fundus is logical, because the LES has similar functions to the fundus, which relaxes to accommodate food during ingestion and preceding emesis, but has quite different functions from the antrum, which provides mixing and propulsion of contents for gastric emptying. The presence of NOS in some LES-projecting neurons may contribute to LES relaxation, as it does in the case of fundic relaxation. The neurologic linkage of vagal fundic and LES relaxation may have clinical relevance, because it helps explain why motor disorders of the LES and fundus frequently occur together.

Animals↗
PubMed2001

World Stress Map of the Earth: a key to tectonic processes and technological applications.

Modern civilisation explores and penetrates the interior of the Earth's crust, recovers from it and stores into it solids, fluids and gases to a hitherto unprecedented degree. Management of underground structures such as boreholes or reservoirs take into account the existing stress either to take advantage of it or at least to minimise the effects of man-made stress. This paper presents the World Map of Tectonic Stresses (in short: World Stress Map or WSM) as a fundamental geophysical data-base. The impact of the WSM is pointed out: in the context of global tectonics, in seismic hazard quantification and in a wide range of technological problems in industrial applications such as oil reservoir management and stability of underground openings (tunnels, boreholes and waste disposal sites).

Earth, Planet↗
PubMed2000

Two novel residues in M2 of the gamma-aminobutyric acid type A receptor affecting gating by GABA and picrotoxin affinity.

An amino acid residue was found in M2 of gamma-aminobutyric acid (GABA) type A receptors that has profound effects on the binding of picrotoxin to the receptor and therefore may form part of its binding pocket. In addition, it strongly affects channel gating. The residue is located N-terminally to residues suggested so far to be important for channel gating. Point mutated alpha1beta(3) receptors were expressed in Xenopus oocytes and analyzed using the electrophysiological techniques. Coexpression of the alpha(1) subunit with the mutated beta(3) subunit beta(3)L253F led to spontaneous picrotoxin-sensitive currents in the absence of GABA. Nanomolar concentrations of GABA further promoted channel opening. Upon washout of picrotoxin, a huge transient inward current was observed. The reversal potential of the inward current was indicative of a chloride ion selectivity. The amplitude of the inward current was strongly dependent on the picrotoxin concentration and on the duration of its application. There was more than a 100-fold decrease in picrotoxin affinity. A kinetic model is presented that mimics the gating behavior of the mutant receptor. The point mutation in the neighboring residue beta(3)A252V resulted in receptors that displayed an about 6-fold increased apparent affinity to GABA and an about 10-fold reduced sensitivity to picrotoxin.

Amino Acid Sequence↗
PubMed2000

Association study of schizophrenia spectrum disorders and dopamine D3 receptor gene: is schizoaffective disorder special?

Alterations in dopamine neurotransmission have been hypothesized to play a role in the etiology of schizophrenia. We considered the dopamine D3 receptor gene on chromosome 3 as a candidate gene for an association analysis. We compared PCR-based genotype markers for healthy controls (n=120) and patients (n=95) with schizophrenia and schizophrenia spectrum disorders as diagnosed by consensus according to DSM-III-R. Our results possibly indicate an association of schizoaffective disorder with DRD3 homozygosity (P=0.056).

Adult↗
PubMed2000

Detection of space-time clusters and epidemiological examinations of scabies in chamois.

In this paper some methodological approaches towards the detection of temporal, spatial and space-time clusters are presented and discussed in context with epidemiological factors of scabies in chamois. This presentation comprises in particular the use of the Scan Test (Wallenstein, 1980) for the detection of temporal clusters and the tests developed by Knox (1964) and Mantel (1967) for the testing of spatiotemporal interactions. Between 1952 and 1998 a total of 1689 cases of scabies in chamois and six cases in ibex were documented in 137 game preserves of the Austrian province of Styria. The evaluations indicate the presence of spatial and temporal clusters. Some possibilities for the spread of scabies in chamois are presented and reveal ibex as a probable vector for scabies transmission between chamois populations. The information may lead to strategies for controlling the spread of the disease.

Animals↗
PubMed2000

GABA(A) receptor assembly. Identification and structure of gamma(2) sequences forming the intersubunit contacts with alpha(1) and beta(3) subunits.

GABA(A) receptors are ligand-gated chloride channels composed of five homologous subunits that specifically recognize one another and assemble around an aqueous pore. To identify domains responsible for the specificity of subunit association, we constructed C-terminal truncated gamma(2) subunits, as well as mutated and chimeric fragments. From their ability to interfere with alpha(1)beta(3)gamma(2) receptor assembly and to associate with full-length subunits, we concluded that amino acid sequences gamma(2)-(91-104) and gamma(2)-(83-90) form the sites mediating assembly with alpha(1) and beta(3) subunits, respectively. Neural network-based secondary structure prediction, Monte Carlo optimization, and hydrophobicity analysis led to the conclusion that these sites also form the intersubunit contacts in the completely assembled receptor and provided important information on the benzodiazepine-binding site and structure of GABA(A) receptors.

Animals↗
PubMed2000

Identification of amino acid residues of GABA(A) receptor subunits contributing to the formation and affinity of the tert-butylbicyclophosphorothionate binding site.

A chimeric GABA(A) receptor subunit was constructed that contained the beta3 sequence from the N-terminus to the first two amino acids of the second transmembrane (TM2) domain. The remaining part of this chimera had the sequence of the alpha1 subunit. On co-expression with alpha1 subunits, this chimera was able to form heterooligomeric channels that were open in the absence of GABA. Picrotoxin and tert-butylbicyclophosphorothionate (TBPS) were able to block these channels with low potency. These channels exhibited high-affinity [3H]muscimol but no high-affinity [35S]TBPS binding sites. Introduction of V251, A252, and L253 of the beta3 subunit into the chimera resulted in the formation of closed channels that could be opened by GABA. The introduction of A252 and L253 of the beta3 subunit into this chimera was sufficient to reconstitute the specific high-affinity [35S]TBPS binding site in receptors composed of the chimera and alpha1 subunits. Replacement of other amino acids of the TM2 region of the chimera with corresponding amino acids of the beta3 subunit modulated the affinity of this [35S]TBPS binding site. Results obtained provide important information on the structure-function relationship of GABA(A) receptors.

Amino Acid Sequence↗
PubMed2000

Non-association of dopamine D4 and D2 receptor genes with personality in healthy individuals.

Recently, different research groups reported conflicting results with regard to an association of dopamine 4 receptor (DRD4) genotypes and the personality dimension of novelty seeking (NS). High scores for NS seemed to be associated with long alleles of a DRD4 polymorphism. Furthermore, an association between personality traits and the dopamine 2 (DRD2) receptor gene was reported. NS and persistence (PS) high scores seemed to be associated with alleles of DRD2. We examined 109 (78 female and 31 male) normal healthy individuals using Cloninger's Temperament and Character Inventory (TCI) in order to replicate these findings. We genotyped a 48 base pair variable number of tandem repeats (from two to eight repeats) polymorphism in the third exon of DRD4 and a Cys311Ser polymorphism in exon 7 of DRD2. We tested alleles and genotypes of DRD4 (allele 7 absent or present; genotype 4,4 versus 4,7), and Ser/Cys and Cys/Cys genotypes of DRD2 for associations with TCI values. NS and the alleles and genotypes of DRD4 did not show any association. In associating the genotypes of DRD2 with TCI scales (NS, harm avoidance, reward dependence and PS), we also found no association. Recent findings associating NS with DRD4 could not be replicated. With regard to DRD2, we tested a different polymorphism as published recently and could not find an association of TCI scales with the gene. The present results therefore do not provide evidence that the DRD2 and DRD4 receptor genes contribute a common and relevant effect to personality traits.

Adult↗
PubMed2000

Genome scan for susceptibility loci for schizophrenia.

OBJECTIVE: Schizophrenia is a relatively common, often chronic and debilitating mental illness. Evidence from various studies has clearly demonstrated that genetic factors contribute substantially to the etiology. The goal of this study was to identify chromosomal regions likely to contain schizophrenia susceptibility genes. METHODS: A genome-wide map of 388 microsatellite DNA markers was genotyped in 5 schizophrenia families. Nonparametric linkage analysis (Genehunter) was used to assess the pattern of allele sharing at each marker locus relative to the presence of disease. RESULTS: Nonparametric linkage scores did not reach a genome-wide level of statistical significance (p < 0.00002) or a p value suggestive of linkage (p < 0.007) for any marker; however, one p value suggested replicated linkage (p < 0.01) at chromosome 6p24 in region D6S309 (p = 0.0047). Furthermore, 11 markers resulted in p < 0.05 at chromosomes 6p, 6q, 10q, 12q and 14q. CONCLUSIONS: Despite the differences in diagnostic schemes, in markers used and methods of analyses between studies published so far, we think that our result supports the notion that there is possibly some consistent evidence for replicated linkage of a schizophrenia susceptibility locus around the region of D6S309 at chromosome 6p24.

Adult↗
PubMed2000

Association studies of candidate genes in bipolar disorders.

The aim of the investigation was to test genes for predisposition to bipolar affective disorder. Therefore, we studied candidate genes in a sample of unrelated patients (n = 102) and healthy controls (n = 79) of Austrian origin, searching for a possible association between polymorphic DNA markers of 5 candidate genes (serotonin transporter, 5-HTT; serotonin 2a receptor, 5-HT2a; dopamine D2 receptor, DRD2; dopamine D3 receptor, DRD3; dopamine transporter, DAT1) and bipolar disorder. There was an association between allelic and genotypic frequencies of 5-HTT and affection status (p = 0.014 and p = 0.017, respectively). However, after correction for multiple comparisons (Bonferroni), these results did not remain significant. Nevertheless, the findings might suggest that alterations in the structure of 5-HTT are involved in the pathogenesis of bipolar disorder, which could have major implications in treatment. No association between 5-HT2a, DRD2, DRD3, DAT1 and bipolar disorder was found.

Adult↗
PubMed2000

[Influence of diagnostic tests for estimating prevalence during surveillance programs].

The influence of diagnostic tests on the estimation of the prevalence and the calculation of sample sizes with respect to different sampling schemes are presented in this paper. These sampling schemes are used for the implementation of surveillance programs. Assuming "perfect tests" (i.e. sensitivity = specificity = 100%) the calculated sample sizes, e.g. for an IBR/IPV-surveillance or a paratuberculosis survey, are half of the sample sizes considering sensitivity and specificity of the diagnostic tests. However the probability not to identify infected livestocks may be 4 times higher neglecting the test characteristics and assuming perfect tests.

Animal Diseases↗
PubMed1999

Possible association between childhood absence epilepsy and the gene encoding GABRB3.

BACKGROUND: Childhood Absence Epilepsy (CAE) is considered to have a predominantly, perhaps exclusively, genetic background. To date, genes responsible for susceptibility to CAE have not been identified. The object of the present study was to test association between CAE and the genes encoding the gamma-aminobutyric acid (GABA) type-A receptor subunits alpha 5 (GABRA5) and beta 3 (GABRB3) located on the long arm of chromosome 15 (15q11-q13). METHODS: A family-based candidate gene approach was applied: 50 Austrian nuclear families ascertained for the presence of an affected child were investigated. GABRA5 and GABRB3 subunit genes were genotyped using DNA gained from peripheral blood samples by Polymerase Chain Reactions (PCR). Genetic association was tested using a Monte Carlo Version of the multi-allele Transmission-Disequilibrium Test (TDT). RESULTS: The TDT displayed significant overall association with GABRB3 (p = .0118). CONCLUSIONS: The present data suggest that the tested polymorphism may be either directly involved in the etiology of CAE or in linkage disequilibrium with disease-predisposing sites.

Adolescent↗
PubMed1999

DNA analysis of Huntington's disease: five years of experience in Germany, Austria, and Switzerland.

OBJECTIVE: To review the direct DNA testing for Huntington's disease (HD) in Germany, Switzerland, and Austria from 1993 to 1997, and to analyze the population with regard to age structure, gender, and family history. METHODS: Twelve laboratories (nine in Germany, two in Austria, and one in Switzerland) recorded data pertaining to repeat number, gender, age at molecular diagnosis, and family history of probands. The molecular test was categorized as either diagnostic (for symptomatic individuals), presymptomatic (for individuals at risk), and prenatal (for pregnancies at risk). RESULTS: A total of 3,090 HD patients, 992 individuals at risk, and 24 fetuses were investigated using DNA analysis. The clinical diagnosis was confirmed in 65.6% of patients. A total of 38.5% of individuals at risk inherited an expanded CAG repeat. The female-to-male ratio showed a distinct predominance of women both in the diagnostic and presymptomatic groups. Of the fetuses tested, six were carriers of an expanded CAG repeat. Two pregnancies were interrupted; one pregnancy was not. No information about the parents' decision was obtained for the remaining three pregnancies. CONCLUSIONS: Approximately 20% of the estimated 10,000 HD patients living in Germany, Switzerland, and Austria have been identified by DNA analysis (total population, approximately 100 million; incidence of HD, 1:10,000). Assuming a ratio of HD patients to individuals at risk of 1:3, approximately 30,000 individuals are, in principle, eligible for a presymptomatic test. Less than 3 to 4% of individuals at risk have requested a presymptomatic test. This shows that the assumed enormous request of predictive testing has not occurred. More surprisingly, prenatal diagnoses were found to be rare.

Adult↗
PubMed1999

A novel serine kinase with specificity for beta3-subunits is tightly associated with GABA(A) receptors.

Tuning of gamma-aminobutyric acid type A (GABA(A)) receptor function via phosphorylation of the receptor potentially allows neurons to modulate their inhibitory input. Several kinases, both of the serine-threonine kinase and the tyrosine kinase families, have been proposed as candidates for such a modulatory role in vivo. However, no GABA(A) receptor-phosphorylating kinase physically associated with the receptor has been identified so far on a molecular level. In this study, we demonstrate a GABA(A) receptor-associated protein serine kinase phosphorylating specifically beta3-subunits of native GABA(A) receptors. The characteristics of this novel kinase clearly distinguish it from enzymatic activities that have been shown so far to phosphorylate the GABA(A) receptor. We putatively identify this protein kinase as the previously described GTAP34 (GABA(A) receptor-tubulin complex-associated protein of molecular mass 34 kDa). Using expressed recombinant fusion proteins, we identify serine 408 as a major target of the phosphorylation reaction, whereas serine 407 is not phosphorylated. This demonstrates the high specificity of the kinase. Phosphorylation of serine 408 is known to result in a decreased receptor function. The direct association of this kinase with the receptor indicates an important physiological role.

Animals↗
PubMed1999

Behavioral effects of tryptophan depletion in seasonal affective disorder associated with the serotonin transporter gene?

There is some evidence that the neurotransmitter serotonin (5-hydroxytryptamine; 5-HT) may be involved in the pathogenesis of seasonal affective disorder (SAD). Short-term tryptophan (TRP) depletion was carried out in 18 drug-free remitted patients who met DSM-IV criteria for SAD. Behavioral effects were measured with the Hamilton Depression Rating Scale (HDRS) both 24 h before and 24 h after TRP depletion. Some of the patients showed behavioral responses such as lowered mood, feelings of guilt, loss of interest, agitation, loss of energy, fatigue, social withdrawal, increased appetite, and carbohydrate craving. It was the aim of our study to investigate whether the genotypes of the serotonin transporter gene were associated with symptoms of transient depressive relapse after TRP depletion. In addition, we matched the SAD patients with healthy control subjects to see if alleles and genotypes of the serotonin transporter gene were associated with SAD. High molecular weight DNA was isolated from peripheral blood leukocytes using standard methods. For the 5-HTT receptor gene, a 17-bp repetitive element of intron 2 was genotyped (variable number tandem repeat, VNTR). Alterations in HDRS scores after TRP depletion showed no significant association with alleles or genotypes of the 5-HTT gene, although heterozygotes showed a trend toward increased HDRS scores. The serotonin transporter is known to play a critical role in the termination of serotonergic neurotransmission by sodium-dependent uptake of 5-HT into the presynaptic neuron. The present study in a small group of SAD patients was unable to demonstrate that the 5-HTT gene plays a role in the pathogenesis of SAD or in short-term depressive relapse after TRP depletion.

Adult↗
PubMed1999

Presence of Staphylococcus aureus with reduced susceptibility to vancomycin in Germany.

A total of 457 Staphylococcus aureus strains from the culture collection of the National Reference Center for Staphylococci in Bonn, Germany, were screened for susceptibility to vancomycin because some Staphylococcus aureus strains are able to form subpopulations that show intermediate resistance to vancomycin. Two methicillin-resistant Staphylococcus aureus strains (isolated in 1993) exhibited intermediate resistance. One of these, Staphylococcus aureus 137-93, which displayed the genomic DNA fragment pattern of the northern German epidemic strain, appeared homogeneously resistant. Neither of these strains had been identified by routine susceptibility testing. The resistance of the German isolates was lower than that of the Japanese isolate Mu50. To determine whether a similar mechanism confers vancomycin resistance in Staphylococcus aureus Mu50 and 137-93, the intracellular cell wall precursor concentration was measured and was not found to be comparably increased in Staphylococcus aureus 137-93. In conclusion, strains showing intermediate resistance have been present in Germany for some time (at least since 1993), but the subpopulations with decreased sensitivity were overlooked during antibiotic susceptibility testing.

Anti-Bacterial Agents↗
PubMed1999

Identification of subunits mediating clustering of GABA(A) receptors by rapsyn.

Human embryonic kidney 293 cells transfected with alpha1beta1gamma2, alpha1beta2gamma2, alpha1beta3gamma2, alpha1beta1, alpha1beta2, alpha1beta3, beta3gamma2, or beta3 subunits formed gamma-aminobutyric acidA receptors on the cell surface that could be clustered by rapsyn. In contrast, alpha1, beta1, beta2, or gamma2 subunits, or alpha1gamma2 subunit combinations could not be detected on the surface of transfected cells and could not be clustered by rapsyn. Experiments investigating the ability of rapsyn to cluster chimeras consisting of the N-terminus of the beta3 subunit and the remaining part of the alpha1, beta2 or gamma2 subunits indicated that the intracellular domains of beta1, beta2, beta3 or gamma2 subunits, but not those of alpha1 subunits are able to form sites mediating clustering by rapsyn. These results demonstrate that rapsyn has the potential to cluster the majority of GABA(A) receptor subtypes via beta or gamma2 subunits. Further experiments will have to clarify the physiological importance of this observation.

Animals↗