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F Leisch

Publications and source records attributed to F Leisch.

At least 19 recordsLinked to original sources

Strain-dependent regulation of neurotransmission and actin-remodelling proteins in the mouse hippocampus.

Individual mouse strains differ significantly in terms of behaviour, cognitive function and long-term potentiation. Hippocampal gene expression profiling of eight different mouse strains points towards strain-specific regulation of genes involved in neuronal information storage. Protein expression with regard to strain- dependent expression of structures related to neuronal information storage has not been investigated yet. Herein, a proteomic approach based on two-dimensional gel electrophoresis coupled with mass spectrometry (MALDI-TOF/TOF) has been chosen to address this question by determining strain-dependent expression of proteins involved in neurotransmission and activity-induced actin remodelling in hippocampal tissue of five mouse strains. Of 31 spots representing 16 different gene products analysed and quantified, N-ethylmaleimide-sensitive fusion protein, N-ethylmaleimide-sensitive factor attachment protein-alpha, actin-like protein 3, profilin and cofilin were expressed in a strain-dependent manner. By treating protein expression as a phenotype, we have shown significant genetic variation in brain protein expression. Further experiments in this direction may provide an indication of the genetic elements that contribute to the phenotypic differences between the selected strains through the expressional level of the translated protein. In view of this, we propose that proteomic analysis enabling to concomitantly survey the expression of a large number of proteins could serve as a valuable tool for genetic and physiological studies of central nervous system function.

Actin-Related Protein 3↗

Internal carotid artery stent placement without emboli protection: results and long-term outcome.

Patients with symptomatic > or = 60% (n = 134), asymptomatic > or = 80% (n = 143), and asymptomatic progressive > or = 60% (n = 25) internal carotid artery stenosis underwent stenting and were followed clinically and by Doppler-assisted duplex imaging for 27.1 +/- 15.6 months. Stroke and death from stroke occurred within 30 days after stenting in 4.7% of the symptomatic and in 3.0% of the asymptomatic patients and in the follow-up period in 2.3% of the symptomatic and in 1.2% of the asymptomatic patients.

Age Factors↗

Coronary angiography in patients undergoing carotid artery stenting shows a high incidence of significant coronary artery disease.

OBJECTIVE: To assess the incidence, morphology, and associated clinical symptoms of coronary artery disease in patients undergoing elective carotid artery stenting. METHODS: In a prospective observational study at a tertiary care centre (university teaching hospital) 444 consecutive patients underwent elective stenting of the carotid artery. Twenty four patients had to be ruled out because of urgent carotid intervention for severe neurological symptoms, lack of compliance, complications from vascular puncture, or renal failure. In 390 patients, the coronary angiography was performed together with carotid artery stenting in a single session; the remaining 30 patients have had a recent coronary angiography. RESULTS: One, two, and three vessel disease and left main stenoses were found in 70 (17%), 64 (15%), 93 (22%), and 31 (7%) patients, respectively. Sixty six (16%) patients had a history of coronary artery disease but no current significant stenosis. Only 39% of the patients with significant stenoses (n = 258) had clinical cardiac symptoms. CONCLUSIONS: For patients undergoing elective stenting of the carotid, routine coronary angiography reliably discloses morphologically significant coronary artery disease and enables consecutive treatment in 61% and 29%. This safe measure is useful because a majority of patients with a significant stenosis are asymptomatic.

Aged↗

No association of clock gene T3111C polymorphism and affective disorders.

CLOCK was hypothesised to be related to susceptibility of affective disorders. To test subsamples of affectively disordered patients, we examined age of onset (AoO), numbers of episodes and melancholic type of clinical manifestation. Using PCR and RFLP, we investigated in patients with unipolar depression and bipolar disorder (BP) whether the CLOCK T3111C SNP is associated with affective disorders (n=102) compared to healthy controls (n=103). No differences were found either in genotype or allele frequency distributions of T3111C polymorphism between patients compared to healthy controls (p>0.2). No deviations from Hardy-Weinberg Equilibrium (HWE) were detected either in patients, or healthy controls. Results suggest that there is no association between the T3111C SNP and affective disorders in general. Data of our sample replicate prior findings of Desan et al. [Am. J. Med. Genet. 12 (2000) 418]. Subsamples of patients with high numbers of affective episodes did show some deviations in genotypes (p=0.0585).

Adult↗

Adhesion and proliferation of human endothelial cells on photochemically modified polytetrafluoroethylene.

We studied the adhesion and proliferation of human endothelial cells on photochemically modified polytetrafluoroethylene samples. The polymer surfaces were modified by exposure to the ultraviolet light of a Xe(2)(*)-excimer lamp at a wavelength of 172 nm in an ammonia atmosphere. Treatment times were between 10 and 20 min. The endothelial cell density was determined 1, 3 and 8 days after seeding by image analysis. Surface modification of the samples resulted in a significant increase in the number of adhering cells and in the formation of a confluent cell layer after 3-8 days. The results were comparable than those obtained on polystyrene Petri dishes, which are used as standard substrates in cell cultivation. Thus modified PTFE appears to be a promising material for the fabrication of artificial vascular prostheses coated with endothelial cells.

Biocompatible Materials↗

A polymorphism (5-HTTLPR) in the serotonin transporter promoter gene is associated with DSM-IV depression subtypes in seasonal affective disorder.

Serotonergic mechanisms are thought to play an important role in the pathogenesis of seasonal affective disorder (SAD). The expression of the serotonin transporter (5-HTT) is regulated in part by an insertion/deletion polymorphism in the serotonin transporter gene promoter region (5-HTTLPR). The 5-HTTLPR short allele (s) has been associated with anxiety-related personality traits and depression, and one study observed an association between the 5-HTTLPR s-allele and SAD and the trait of seasonality. We genotyped 138 SAD patients and 146 healthy volunteers with low seasonality for 5-HTTLPR. No difference between patients and controls was found for genotype distribution and s-allele frequency. However, genotype distribution and allele frequencies were strongly associated with DSM-IV depression subtypes. Melancholic depression was associated with the 5-HTTLPR long (l) allele and atypical depression with the 5-HTTLPR s-allele (two-sided Fisher's exact test: genotype distribution: P=0.0038; allele frequencies: P=0.007). Our data are compatible with the hypothesis of a disease process that is not causally related to 5-HTTLPR, but involves 5-HT neurotransmission and 5-HTTLPR somewhere on its way to phenotypic disease expression.

Bipolar Disorder↗

Study of family history in seasonal affective disorder.

OBJECTIVE: In our investigation we assessed the risk of morbidity for psychiatric disorders among the first-degree relatives of patients with seasonal affective disorders (SAD) and compared it with a control group of patients suffering from nonseasonal mood disorders (NSMD). METHODS: Over a period of 12 months (June 1994 to May 1995) we recruited patients consecutively admitted to our psychiatric university outpatient clinic in a prospective study. All patients were diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, revised 4th edition. A total of 344 patients presented themselves with a diagnosis of affective disorder. Out of these, 36 were diagnosed as having SAD. From the same group of 344 patients, we selected a matched control group of 36 patients suffering from NSMD. The experimental and control groups were matched according to sex, age, severity of illness and number of siblings. RESULTS: There was no significant difference concerning the lifetime prevalences for psychiatric disorders among the fist-degree relatives in both groups (SAD = 16.5% and NSMD = 19%). CONCLUSION: It seems that there is no difference in familiarity for psychiatric disorders between SAD and NSMD.

Adult↗

[Percutaneous interventions combined with carotid artery stenting].

BACKGROUND AND OBJECTIVE: Although the value of interventional treatment of arterial stenosis has not been confirmed for all sites by randomized studies, these methods are used more and more, often for several arteries simultaneously. This study reports results of percutaneous carotid artery stenting combined with simultaneous interventions in other central arteries. PATIENTS AND METHODS: Among 90 patients who had undergone percutaneous carotid artery stenting, 13 had simultaneous intervention in other arteries: contralateral carotid artery (n = 4), ipsilateral common carotid artery near its aortic origin (n = 1), left subclavian artery (n = 1), coronary artery (n = 6) and one of both carotid arteries and a coronary artery. RESULTS: Primary success (restenosis < 30%) was achieved in all cases. Additional carotid artery stenting was done in 18. Stents were also implanted in eight coronary arteries, angioplasty without stenting in two. Mean stenosis of the carotid arteries was reduced from 85 +/- 10% to 3 +/- 6%, that of the coronary arteries from 90 +/- 10% to 9 +/- 10%. Serious complications, a major stroke, occurred in one of the 13 patients (7.7%). Minor complications were seen in two patients: transitory ischaemic attack in one, small myocardial infarction in the other. CONCLUSION: Carotid artery stenting combined with simultaneous intervention in other central arteries can be done with a high rate of success and relatively few complications. This form of treatment should be considered in selected patients.

Aged↗

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↗

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↗

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↗

Stationary and integrated autoregressive neural network processes.

We consider autoregressive neural network (AR-NN) processes driven by additive noise and demonstrate that the characteristic roots of the shortcuts-the standard conditions from linear time-series analysis-determine the stochastic behavior of the overall AR-NN process. If all the characteristic roots are outside the unit circle, then the process is ergodic and stationary. If at least one characteristic root lies inside the unit circle, then the process is transient. AR-NN processes with characteristic roots lying on the unit circle exhibit either ergodic, random walk, or transient behavior. We also analyze the class of integrated AR-NN (ARI-NN) processes and show that a standardized ARI-NN process "converges" to a Wiener process. Finally, least-squares estimation (training) of the stationary models and testing for nonstationarity is discussed. The estimators are shown to be consistent, and expressions on the limiting distributions are given.

Artifacts↗

[Secondary prevention following coronary intervention. Survey of 13 intervention centers in Austria].

Risk factor control has been shown to reduce the incidence of coronary events in patients with or without preceding infarction. Secondary prevention should therefore be borne in mind by every cardiologist. In order to test this concept and/or to promote secondary prevention in our country, the following survey was conducted by our working group for epidemiology and prevention. All interventional centres of the country (7 million inhabitants) were asked to report relevant data of 50 consecutive patients with PTCA in a structured questionnaire. Thirteen centres responded and we report the data of 650 patients. The mean proportion of women was 28%, the mean age 61.1 years and the mean stent rate 49.8%. The indications for PTCA varied widely: stable angina 10-74%, unstable angina 10-86%, primary PTCA 0-22%. The risk factor history was distributed as follows: diabetes 12-46% (mean 22.3%), hypertension 32-68% (mean 54.2%), current smoking 6-56% (mean 21.9%), and total cholesterol (TChol) > 200 mg/dl: 30-78% (mean 60.3%). Current lipid values were available for T chol. in 44-100% (mean 84.5%) and for LDL in 4-100% (mean 67.1%). Dietary counselling by a dietician was done in 4-100% of patients (mean 35.6%) Information concerning the hazards of smoking was given to 25-100% (mean 83.6%) of current smokers. Drug treatment at hospital discharge was as follows: 84-100% (mean 93.1%) received ASA, 24-74% (mean 49.8%) ticlopidine, 6-84% (mean 53.3%) nitrates, 34-82% (mean 60.2%) beta blockers, 10-70% (mean 39.5%) ACE inhibitors, 4-74% (mean 4 7.2%) lipid lowering drugs, 7-48% (mean 17.8%) calcium antagonists, 0-12% (mean 6.1%) digitalis and 0-28% (mean 13.6%) diuretics. Follow-up data were collected in 4 centres at 6 months post discharge and were available for 174 patients. Here we found an increase in the prescription of calcium antagonists, digitalis and statins. The following conclusions were drawn at a conference in which all centres participated: lipid values should be available for each patient at PTCA, dietary counselling should be initiated for every patient during hospitalisation (and continued by the family physician) and the national cardiac society should promote guidelines for the use of drugs in which the variation in use is too wide at present. It should be ensured that these guidelines are implemented not only in patients after AMI but also in those after PTCA.

Adrenergic beta-Antagonists↗

[Carotid stenting: acute results and complications].

The treatment of carotid stenoses with balloon angioplasty and stenting is a new and not generally established method. During a one year period 65 patients (22 female, 43 male, mean age: 73 years, 47 with neurologic symptoms, 8 with contralateral carotid occlusion) with significant (>70%) carotid stenosis were treated with balloon angioplasty and balloon expandable stents. The primary technical success rate was 98% (65/66 patients) respectively 99% (69/70 stenoses). A combined procedure was performed in 11 /17%) patients with stenting in both carotid arteries in 4 patients with additional coronary interventions in 6 patients and stenting of the origin of the common carotid artery in one patient.Severe neurologic complications occurred in 4 (6.2%) patients (1 death, 1 major stroke, 2 minor strokes) and short lasting neurologic deficits in additional 4 (6.2%) patients. Cardiovascular complications were not observed. Local (inguinal) problems occurred in 3 (4.5%) patients (2 aneurysma spuria, 1 transfusion for hematoma). Frequently, balloon insufflation was associated with bradycardia (40%) and additional hypotension (11%). In summary, carotid stenting can be performed with technically high success rates (99%), but it is adversely influenced by not infrequent thromboembolic cerebral events (12.4%). The possibility to perform combined procedures with interventions in other vessels (both carotid arteries, coronary arteries, aortic arch arteries) is advantageous.

Aged↗

[Elective stenting of "unprotected" left main coronary stenosis in patients without contraindication to bypass surgery].

Coronary surgery is at this point of time the standard therapy of unprotected left main coronary artery stenosis. Coronary angioplasty (PTCA) is performed only in bail out situations. The number of publications of successful percutaneous intervention in unprotected left main coronary stenosis is increasing because of increasing use of stents and ticlopidine to avoid stent-thrombosis. From 9/96 to 7/98, 13 patients with unprotected left main coronary stenosis were treated with stents. All of them were accepted by the heart surgeon for bypass surgery but were not considered to be optimal candidates due to advanced age of more than 80 years (n = 5), significant co-morbidity (n = 2) or diffuse diseased peripheral coronary segments (n = 6). Mean age of patients was 74 +/- 10 years, 9 were male, and all patients presented with angina III-IV (CCS). Mean ejection fraction was 55 +/- 15%. Localization of stenoses were classified as ostial (n = 5), middle (n = 3), and bifurcational (n = 6). One patient had stenoses both in the ostium and in the bifurcation. In all cases a PTCA of the culprit stenosis was performed prior to stent implantation. The mean diameter of the stents used was 3.3 +/- 0.3 mm and the mean length was 11 +/- 4 mm. In 6 patients a PTCA of either left anterior descendens (LAD) or right coronary artery was performed in the same session. In 4 of these patients it was followed by a stent implantation. All procedures were performed with surgical stand-by, an intraaortal balloon pump was available, but was not uses prophylactically. Stent implantation could be performed successfully in 12 out of the 13 patients (success rate 92%). In bifurcational stenoses stents were positioned with the proximal end in the left main and the distal end in the LAD. Significant injury or occlusion of the circumflex artery was not observed. In one patient with bifurcational stenosis with severe calcification it was not possible to cross the lesion with an accurate sized balloon. Trying to cross with a smaller balloon (2.5 mm) resulted in dissection of the left main coronary artery which could not be reopened again by catheter technique. This patient was transferred to the operating room under conditions of cardiopulmonary resuscitation and a bypass surgery was performed. He was dismissed from the hospital with no evidence of perioperative myocardial infarction. The mean time for follow-up was 12 +/- 7 months, all patients are still alive. In 6 patients an angiography was performed during follow-up because of suspicion of recurrent ischemia. Two patients out of these 6 had restenoses in the left main coronary artery which were re-dilated (17%). Another 2 patients had stenoses in other coronary segments and were also dilated. Thus, stenting of left main coronary artery stenoses is feasible, however, with acceptable risks and could be considered in selected patients as an alternative to coronary artery surgery.

Aged↗