Investigation of the ICAM-1 G241A and A469G gene polymorphisms in schizophrenia.
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Biomedical subjects
Publications and source records attributed to S Behrens.
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Magnetocardiography provides touchless information about myocardial excitation propagation and repolarization. This evolving diagnostic technique has been used so far to risk-stratify patients in terms of sudden cardiac death and to detect myocardial ischemia. We evaluated its potential to assess myocardial viability in patients with coronary artery disease. Magnetocardiography was performed using a shielded prototype 49-channel LTS SQUID system. A specific algorithm was developed to calculate automatically a set of magnetocardiographic parameters. Regional myocardial viability was determined using 18F-labeled fluoro-2-deoxyglucose positron emission tomography. We found that magnetocardiography may contribute essentially to discriminate between viable myocardium and infarct scar.
OBJECTIVE: To study the site of the ischemic lesion, the underlying cause, and the prognosis of acute stroke with distal arm paresis. METHOD: The authors investigated 14 consecutive patients with acute distal arm paresis with a diagnostic stroke protocol and early MRI, including T2-weighted images, diffusion-weighted images (DWI), and perfusion-weighted images (PWI). Acute DWI lesions were shown on coregistered T2-weighted images for analysis of the exact anatomic lesion location. RESULTS: Patients showed a uniform (7/14), radial (3/14), or ulnar (4/14) distribution of hand paresis. In all cases, DWI identified small lesions located in the motor cortex. Topographic lesion analysis, which was correlated with the clinical deficit, showed lesions centered in the hand knob area (2/14), involving the lateral (6/14), medial (4/14), or both (2/14) borders of the hand knob. PWI (calculated time-to-peak maps) did not show a mismatch between the DWI lesion and the PWI lesion. In six patients, DWI and PWI lesions were identical in size and location; no definite perfusion deficit was seen in eight patients. In agreement with PWI, no patient showed clinical worsening, and six patients recovered completely within a week. Further investigations showed a potential source of embolus in 11 cases. CONCLUSIONS: Acute ischemic distal arm paresis is usually caused by a small cortical lesion in the motor hand cortex attributable to distal Rolandic artery obstruction without additional tissue at risk. These findings confirm the observed benign clinical course and its apparent main cause (artery-to-artery or cardiac embolism).
The Escherichia coli periplasmic peptidyl-prolyl isomerase (PPIase) SurA is involved in the maturation of outer membrane porins. SurA consists of a substantial N-terminal region, two iterative parvulin-like domains and a C-terminal tail. Here we show that a variant of SurA lacking both parvulin-like domains exhibits a PPIase-independent chaperone-like activity in vitro and almost completely complements the in vivo function of intact SurA. SurA interacts preferentially (>50-fold) with in vitro synthesized porins over other similarly sized proteins, leading us to suggest that the chaperone-like function of SurA preferentially facilitates maturation of outer membrane proteins.
BACKGROUND: The identification of patients at increased risk for ventricular tachycardia or ventricular fibrillation (VT/VF) and sudden cardiac death has consequences for therapeutic options and thus may reduce mortality in patients with coronary artery disease (CAD). HYPOTHESIS: We hypothesized that the intra-QRS fragmentation in magnetocardiographic recordings is increased in patients with CAD and with a history of VT/VF. METHODS: Multichannel magnetocardiography (MCG) was carried out in 34 healthy controls, 42 patients with CAD without a history of VT/VF, and 43 patients with CAD and with a history of VT/VF. The intra-QRS fragmentation was quantified by a new fragmentation score. Its spatial distribution was investigated using two-dimensional (2-D) contour maps according to the sensor position of the 49-channel magnetogradiometer. RESULTS: Patients with CAD and with a history of VT/VF had significantly increased QRS fragmentation compared with patients with CAD without VT/VF or controls (72.9+/-37.5, 48.5+/-14.3, and 42.5+/-7.8, respectively: p <0.05). The area of high fragmentation in 2-D contour maps was twice as large in patients with than in those without a history of VT/VF (represented by the number of MCG channels with high fragmentation: 26.3+/-15.5 vs. 12.4+/-9.9, p<0.0001). Patients prone to VT/VF could be identified with a sensitivity of 64% and a specificity of 90%. CONCLUSION: In patients with CAD and with a history of VT/VF, intra-QRS fragmentation is increased and the area of high fragmentation in 2-D contour maps is enlarged. These findings may be helpful in identifying patients with CAD at risk for malignant tachyarrhythmias.
Antiepileptic drug (AED)-induced side effects still may hinder antiepileptic therapy. We describe a 38-year-old woman with complex focal seizures. Due to normal neuroradiological findings and the lack of evident pathogenetic factors, we diagnosed cryptogenic epilepsy. In response to cognitive side effects, the initial therapy with phenobarbital was replaced by phenytoin treatment only. Subsequent MRI investigation showed a hyperintense lesion in the corpus callosum without gadolinium enhancement. Responding to an increase in seizure frequency (SF), phenytoin was replaced first by lamotrigin monotherapy and then by additional valproate treatment. An MRI follow-up investigation did not show the previously described lesion of the corpus callosum, thus suggesting phenytoin-induced extrapontine myelinolysis. In the literature, vigabatrin-induced demyelinization of the corpus callosum has also been described. In patients treated with the AEDs phenytoin or vigabatrin who demonstrate increased SF, such a side effect should be taken into account and MRI investigation performed.
Two recently described polymorphisms in the promoter region of the apolipoprotein E (APOE), the -491A/T and Th1/E47csT/G polymorphism, have been suggested to be associated with an increased risk for Alzheimer's disease (AD) independent from the APOE epsilon 4 carrier status. We studied the association between the APOE epsilon 4 polymorphism and the -491A/T and Th1E47csT/G polymorphisms in a sample of 118 healthy, non-demented controls and 239 consecutively recruited gerontopsychiatric patients diagnosed as: Alzheimer's disease (N = 89), age mild cognitive impairment (N = 32), memory complainers without any cognitive deficit (N = 54) and depression/other psychiatric disorders (N = 64), to test whether the investigated polymorphisms have a high enough selectivity and specificity to distinguish between the different gerontopsychiatric disorders or to differentiate AD genetically from other forms of dementia, respectively. Also a possible association with the APOE epsilon 4 polymorphism was examined. We found a statistically significant association between the APOE epsilon 4 allele and Alzheimer's disease (p = 0.0001) and age associated memory impairment (p = 0.006). Our study failed to show an association between the promoter polymorphisms -491A/T and Th1E47csT/G in the APOE gene and gerontopsychiatric disorders either alone or in relationship to the APOE epsilon 4 polymorphism. However, if we combine our results with three previous published positive reports there seems to be an association between the -491A/T polymorphism and AD, though its size is less than found in the original publication.
UNLABELLED: Despite the fact that botulism was described in Germany for the first time by Kerner in 1820, the disease is almost forgotten in this country. Only about 10-20 cases of classical botulism (intoxication) are recorded every year, including 1-2 cases of clinical infant botulism. As we assumed a high incidence of botulism to be connected with cases of sudden infant death (SID), we undertook the research work presented here. From every case of unexpected infant death up to 12 months of age, standardised specimens (blood, liver and intestine) were taken at autopsy. They were tested for the presence of botulinum neurotoxin (BoNT) and/or bacterial forms of Clostridium botulinum with subsequent BoNT neutralisation tests by the international standard mouse bioassay. Age, sex, pathological findings and season were recorded. Over a 5-year period, 75 samples including 57 SID cases were tested. Free toxin was found in nine and bacterial forms were detected in six samples. Toxin neutralisation revealed the definite presence of BoNT/BoNT producing bacteria (mainly type E), whereas another 11 toxin tests were inconclusive. According to international literature, these 15 cases are to be interpreted as infant botulism. CONCLUSION: the results show a remarkable incidence of infant botulism without any known previous medical history, partly hidden as sudden infant death. We propose to systematically search for botulism in connection with sudden infant death.
Success of stroke treatment with rt-PA depends on rapid vessel recanalization. Enzymatic thrombolysis may be enhanced by additional transcranial application of ultrasound (US). We investigated this novel technique using a 185-kHz probe and compared it to standard diagnostic US. In vitro studies were performed in a continuous pressure tubing system. Clots were placed in a postmortem skull and treated with rt-PA together with or without transtemporal 185-kHz US insonation (2W/cm(2)) and in comparison to 1-MHz diagnostic US (0.5 W/cm(2)). Recanalization time was significantly (p < 0.01) shorter in the 185-kHz (14.1 min) and 1-MHz (17.1 min) US rt-PA treatment group compared to rt-PA treatment alone (29.3 min.). Flow rate was significantly higher (p < 0.025) and increased faster in the combined treatment group with rt-PA + 185-kHz US compared to rt-PA + 1-MHz US. We investigated the blood-brain barrier in rats after 90-min exposure time of the brain with 185-kHz US, but no damage was observed. Results suggest efficacy and safety of the 185-kHz transducer, which is superior to diagnostic US. Such a novel US probe may be able to optimize thrombolytic stroke treatment.
Fluorescence in situ hybridisation (FISH) with rRNA-targeted oligonucleotide probes facilitates the rapid and specific identification of individual microbial cells in their natural environments. Over the past year there have been a number of methodological developments in this area and new applications of FISH in microbial ecology and biotechnology have been reported.
Systemic treatment with rtPA approved for a 3-hour window is the only established causal therapy for acute stroke in the United States and Canada. Thrombolytic therapy with rtPA demonstrated a small, although significantly reduced morbidity, in a limited number of highly selected patients. As recently shown, intraarterial application is favorable and opens the window of treatment up to 6 hours. The combination of ultrasound with thrombolytic agents may further enhance the potential benefit by means of enzymatic-mediated thrombolysis, which has been demonstrated in different in vitro and in vivo experiments for an accelerated recanalization of occluded peripheral and coronary vessels. Whereas no or only small attenuation of ultrasound can be expected through skin and chest, intensity will be significantly attenuated if penetration of the skull is required. The transcranial penetration of ultrasound increases when the frequency is decreased to 20 kHz and may be transmitted through the skull transtemporally with tolerable attenuation up to 200 kHz. This results in efficacy in vitro with low intensities of 0.5-2.0 W/cm(2) systemic treatment with rtPA approved for a 3-hour window in the nonfocused ultrasound field. Application of ultrasound insonation increased rtPA-mediated thrombolysis up to 20% in a static model; meanwhile, it enhanced the recanalization rate from 30%-90% in a flow model. In vitro results suggest that 1 MHz ultrasound with 0.5 W/cm(2), established for diagnostic purposes, may already enhance rtPA- mediated thrombolysis. Before therapeutic ultrasound can be tested clinically in acute stroke, safety of transcranial exposure of the brain has to be confirmed. To date, animal experiments suggested no harm to the blood brain barrier or systemic heating with 2 W/cm(2). This combined treatment is one perspective in optimizing therapy in acute stroke within the acute phase and may be applied easily with few limitations.
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OBJECTIVE: Current management of acute stroke is characterised by an aggressive approach including specific therapy i. e. reperfusion therapy. However currently stroke patients often arrive too late in hospitals offering adequate treatment. Therefore optimized logistics play a predominant role in modern stroke management. AIMS OF THE STUDY: 1. Does teaching of EMS staff and the public result in reduced prehospital latencies 2. Will EMS personnel be able to effectively screen patients potentially suitable for thrombolysis? METHODS: During a six week-period all EMS patients presenting with possible signs of an acute stroke were prospectively registered (period 1). Data of interest were age, mode of primary contact, prehospital latencies, mode of transportation, destination and final diagnosis. Next an algorithm was established allowing EMS personnel to transfer patients with an assumed stroke to the best suitable hospital. Teaching comprised clinical signs, indication of CT scanning, pathophysiology, specific therapeutic options (thrombolysis), and criteria to identify patients suitable for thrombolysis. In a second step the public was continuously taught about stroke symptoms and the necessity to instantly seek EMS assistance. After 12 months data were compared to baseline (period 2). RESULTS: (period 2 vs. Period 1): Rate of patients transferred to a stroke center: 60 % vs. 54 %; rate of those transported to hospitals not offering CT scans: 17 % vs. 26 % (p < 0.05). Percentage of patients primarily contacting the EMS system: 33 % vs. 24 %. Median interval between onset of symptoms and emergency call: 54 vs. 263 minutes Median interval between the emergency call and arrival at the emergency department: 44 vs. 58 minutes (p < 0.01). Rate of patients admitted with a diagnosis other than stroke: 18 % vs. 25 % (n. s.). Median interval between onset of symptoms and hospital admission: 140 vs. 368 minutes (p < 0.001). Median age: 69 vs. 75 years (p < 0.01). CONCLUSION: This study demonstrates the efficacy of educational efforts in reducing latencies and in screening patients potentially suitable for thrombolysis. Future efforts will comprise more intense education of a high risk subpopulation.
Clostridium acetobutylicum DSM 792 accumulates and phosphorylates mannitol via a phosphoenolpyruvate (PEP)-dependent phosphotransferase system (PTS). PEP-dependent mannitol phosphorylation by extracts of cells grown on mannitol required both soluble and membrane fractions. Neither the soluble nor the membrane fraction could be complemented by the opposite fraction prepared from glucose-grown cells, indicating that the mannitol-specific PTS consists of both a soluble (IIA) and a membrane-bound (IICB) component. The mannitol (mtl) operon of C. acetobutylicum DSM 792 comprises four genes in the order mtlARFD. Sequence analysis of deduced protein products indicated that the mtlA and mtlF genes respectively encode the IICB and IIA components of the mannitol PTS, which is a member of the fructose-mannitol (Fru) family. The mtlD gene product is a mannitol-1-phosphate dehydrogenase, while mtlR encodes a putative transcriptional regulator. MtlR contains two PTS regulatory domains (PRDs), which have been found in a number of DNA-binding transcriptional regulators and in transcriptional antiterminators of the Escherichia coli BglG family. Also, near the C-terminus is a well-conserved signature motif characteristic of members of the IIA(Fru)/IIA(Mtl)/IIA(Ntr) PTS protein family. These regions are probably the sites of PTS-dependent phosphorylation to regulate the activity of the protein. A helix-turn-helix DNA-binding motif was not found in MtlR. Transcriptional analysis of the mtl genes by Northern blotting indicated that the genes were transcribed as a polycistronic operon, expression of which was induced by mannitol and repressed by glucose. Primer extension experiments identified a transcriptional start point 42 bp upstream of the mtlA start codon. Two catabolite-responsive elements (CREs), one of which overlapped the putative -35 region of the promoter, were located within the 100 bp upstream of the start codon. These sequences may be involved in regulation of expression of the operon.
Recent reports have suggested that genetic polymorphisms in the alpha-2 macroglobulin (A2M) gene are associated with an increased risk for Alzheimer's disease. In the present study we tested two polymorphisms in the alpha-2 macroglobulin gene, a 5 bp deletion at the 5' splice site of exon 18 and a G/A point mutation (V1000I) in exon 24, in a sample of 118 healthy, non demented controls and 238 consecutively recruited gerontopsychiatric patients, diagnosed as: Alzheimer's disease (N=88), mild cognitive impairment (N=32), subjective cognitive complaints (N=54) and depression/other psychiatric disorders (N=64). The aim of this study was to test whether the investigated polymorphisms has a high enough selectivity and specificity to distinguish between the different gerontopsychiatric disorders or to differentiate genetically AD from other forms of dementia, respectively. Also a possible relation to the APOE varepsilon4 polymorphism was examined. Our study failed to show an association between the two investigated polymorphisms in the alpha-2 macroglobulin gene and any of the four different psychogeriatric patient subgroups, either alone or in combination with the APOE varepsilon4 genotype.
The aim of this study was to investigate [3H]paroxetine binding and impulsivity in alcohol-dependent and age-matched control subjects in relation to a 5'-promoter region serotonin transporter (5-HTT) polymorphism (5-HTTLPR). Alcohol-dependent subjects were hypothesized to show a decreased number of bindings sites and a lower dissociation constant. 5-HTTLPR S-genotype carriers in both alcohol-dependent and control subjects were expected to show significantly fewer binding sites and a lower dissociation constant. Influences of impulsive traits, chronic daily alcohol intake, duration of alcohol dependence, age of onset and age on [3H]paroxetine binding were also investigated. Inpatients meeting DSM IV alcohol dependence criteria and of German descent were recruited to avoid ethnic stratification effects. One hundred and seventeen control subjects of similar social status were recruited from a town community. Blood samples were taken from both alcohol-dependent and control subjects to determine 5-HTTLPR genotypes using PCR of lymphocyte DNA, and to perform platelet [3H]paroxetine binding (binding capacity: B(max); and dissociation constant: K(D)). Impulsivity was assessed using the Barratt impulsiveness scale version 5 (BIS-5) in alcohol-dependent subjects only. Alcohol-dependent subjects were subdivided into low or high impulsivity groups using a median-split of the BIS-5 scale. The control group was slightly older than the alcohol-dependent group (not statistically significant). [3H]paroxetine binding was investigated in 72 control subjects and 72 patients, of which five patients met type 2 alcohol dependence criteria. Genotyping was carried out in all patients and control subjects. A significant influence of duration of alcohol dependence was found on the [3H]paroxetine binding K(D) but not B(max.) Neither alcohol-dependent nor control subjects showed any differences in B(max) or K(D). S-allele carriers did not show a decreased binding or lower dissociation constant. Furthermore, no significant interaction between B(max) and K(D) with either 5-HTTLPR genotype or impulsivity was revealed. This was the first study to investigate platelet [3H]paroxetine binding in alcohol-dependent and age-matched control subjects in relation to the 5-HTTLPR genotype. No differences concerning 5-HTTLPR-alleles were found in these groups Furthermore, no significant interaction between these parameters and impulsivity was shown in alcohol-dependent subjects. These results do not support previous results of altered [3H]paroxetine binding sites in alcohol-dependent subjects or 5-HTTLPR S-allele carriers. K(D) might be influenced by duration of alcohol dependence, but not sufficiently to yield differences between alcohol-dependent and control subjects.