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Biomedical subjects

S Behrens

Publications and source records attributed to S Behrens.

At least 19 recordsLinked to original sources
PubMed2001

The SurA periplasmic PPIase lacking its parvulin domains functions in vivo and has chaperone activity.

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.

Bacterial Proteins↗
PubMed2001

Molecular analysis of the mannitol operon of Clostridium acetobutylicum encoding a phosphotransferase system and a putative PTS-modulated regulator.

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.

Amino Acid Sequence↗
PubMed2000

Polymorphisms in the alpha-2 macroglobulin gene in psychogeriatric patients.

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.

Aged↗
PubMed2000

Serotonin transporter gene regulatory region polymorphism (5-HTTLPR), [3H]paroxetine binding in healthy control subjects and alcohol-dependent patients and their relationships to impulsivity.

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.

Adult↗
PubMed2000

[Mechanism of induction and termination of ventricular fibrillation--significance of dispersion of ventricular repolarization].

It has been known for many years that ventricular fibrillation may be induced and terminated by electrical field stimuli. Recent experimental studies have shown that both fibrillation and defibrillation have a common electrophysiologic mechanism that is based on the interaction between the electrical field stimulus and ventricular repolarization. Ventricular fibrillation will be induced if the field stimulus is applied with the area of vulnerability, this area of vulnerability is defined two dimensionally by the shock coupling interval and shock strength, and is modified by the configuration of the shock. A field shock that is applied within the area of vulnerability causes heterogeneity of ventricular repolarization immediately after the shock (postshock dispersion), thereby enabling the development of circuit movements and reentry, and resulting in ventricular fibrillation. High energy shocks, however, that are applied above the area of vulnerability (i.e., above the upper limit of vulnerability) will not induce ventricular fibrillation due to homogeneous prolongation of repolarization and a resulting small postshock dispersion. In analogy, ventricular fibrillation will continue after unsuccessful low-energy defibrillation shocks due to high postshock dispersion, whereas a high-energy shock will synchronize ventricular repolarization, thereby causing small postshock dispersion and termination of ventricular fibrillation. This paper describes the relation between fibrillation, defibrillation and ventricular repolarization based on experimental findings. A possible clinical application of these findings is that the upper limit of vulnerability may be used as a surrogate for the defibrillation threshold. Thus, defibrillation threshold testing may not be necessary during future implantations of automatic cardioverter defibrillators.

Defibrillators, Implantable↗
PubMed2000

Chronic sclerodermic graft-versus-host disease refractory to immunosuppressive treatment responds to UVA1 phototherapy.

Graft-versus-host disease is a frequent complication of allogenic bone marrow transplantation. Approximately 10% of patients suffering from chronic graft-versus-host disease develop sclerodermic graft-versus-host disease of the skin, which often does not respond to conventional immunosuppressive therapy. An alternative to immunosuppressive treatment is photochemotherapy. We describe a patient with chronic sclerodermic graft-versus-host disease who did not respond to a combination therapy of cyclosporine and prednisone and later mycophenolate mofetil plus prednisone. A combination therapy of mycophenolate mofetil (2 g/day) and low-dose UVA(1) therapy (single dose, 20 J/cm(2), 4 times per week over 6 weeks) resulted in striking clinical improvement of sclerodermic graft-versus-host disease.

Adult↗
PubMed2000

Combination phototherapy of psoriasis with narrow-band UVB irradiation and topical tazarotene gel.

BACKGROUND: Narrow-band UVB (311 nm) phototherapy offering an emission spectrum closely conforming to the peak of the action spectrum for clearing psoriasis has significantly improved phototherapy for psoriasis. Because the majority of the commonly used topical therapies in treatment of psoriasis have limitations, a need for new topical agents remains. Tazarotene has been shown to be efficacious in plaque-type psoriasis. Combination of narrow-band UVB with topical agents has been shown to enhance efficacy of both treatment modalities. OBJECTIVE: We attempted to evaluate the efficacy of narrow-band UVB phototherapy in combination with topical tazarotene. METHODS: Ten patients with stable plaque psoriasis were treated with narrow-band UVB. In addition, topical tazarotene 0.05% was applied once daily to one side of the body. The follow-up period was 4 weeks. Efficacy was assessed separately for both body halves by means of a modified Psoriasis Area and Severity Index (PASI). RESULTS: Both treatment modalities notably reduced the PASI scores with values being significantly lower in skin areas treated with narrow-band UVB phototherapy in combination with topical tazarotene. CONCLUSION: The addition of tazarotene to narrow-band UVB phototherapy promotes more effective, faster clearing of psoriasis compared with UVB (311 nm) monotherapy.

Administration, Cutaneous↗
PubMed2000

Acceleration of thrombolysis with ultrasound through the cranium in a flow model.

Thrombolysis is an efficient therapy for hyperacute stroke within a limited time window. Neurological outcome depends on the recanalization time of the occluded vessel. Nonthermal effects of low-frequency ultrasound (US) accelerate enzymatic fibrinolysis in vitro. We examined the effects of transcranially applied US on recombinant tissue plasminogen activator (rt-PA)-mediated thrombolysis in a flow model in vitro. Pure fibrin clots were placed in a continuous-pressure flow model and treated with rt-PA during 1-MHz US exposure (0.5 W/cm(2); spatial peak, temporal peak intensity). Transcranial and direct US application in combination with rt-PA significantly (p<0.001) shortened recanalization time, increased perfusion flow and reperfusion rate in comparison with rt-PA-mediated thrombolysis alone. Recanalization rate within 30 min was 90-100% in the US-exposed clots vs. 30% in the clots treated only with rt-PA. Our results suggest that transcranial application of 1-MHz US may accelerate reperfusion and recanalization rate of occluded intracerebral vessels by enhancing rt-PA-mediated thrombolysis. Shortening of recanalization time could contribute to optimizing effects of acute thrombolytic stroke therapy.

Blood Flow Velocity↗
PubMed2000

[3-D localization of cardiac structures in real time].

Radiographic 3-D localisation enables measurements to be made that facilitate the placement of the interventional device during cardiac intervention. To enable the reader to implement the method himself, we describe the computation of 3-D coordinates, acquisition of the imaging and projection data on-line, and the accuracy that can be expected with the method. The 3-D coordinates of a cardiac structure are calculated from the image point coordinates, the projection data and the system constants of a biplane isocentric X-ray unit. Technical imaging errors are corrected a priori. The biplane projection data of a run are acquired on-line and stored in a data base. The image pair of interest is identified automatically from the inscribed run number, and assigned to the projection data from the data base. The target image point is marked on the monitor for 3-D localisation. The accuracy of the method was determined by comparing the calculated and actual cross-sectional points of a centimetre grid imaged in biplane X-ray projections. 3-D localisation took an average of 9.8 +/- 1.2 seconds. Angles and distances were assessed with a standard error of 1.1 degrees and 0.8 mm. The run number is identified correctly in 98.5% of the cases. The mean absolute location error for all points and image pairs was 0.61 +/- 0.32 mm. The accuracy and precision was 0.03 +/- 0.40 mm. Radiographic 3-D localisation can be performed readily and accurately on-line. The results obtained with the method enable interventional decisions to be optimized.

Computer Graphics↗
PubMed2000

Identification of two genes encoding putative new members of the ECF subfamily of eubacterial RNA polymerase sigma factors in Clostridium acetobutylicum.

Two genes from Clostridium acetobutylicum DSM 792 were identified which are predicted to encode new members of the ECF subfamily of eubacterial RNA polymerase sigma factors. The sigX gene has the potential to encode a 184-amino acid protein with a molecular mass of 21,870 Da and with the highest overall similarity to Fecl of Escherichia coli (27 % identical residues). The second gene, which is predicted to encode an alternative sigma factor of the ECF subfamily, is the previously described orf2 gene (Gerischer and Dürre, 1990) located in the adc gene region of C. acetobutylicum. The deduced protein of orf2 has significant similarity to SigX of C. acetobutylicum (22 % identical residues) and shares structural features with other alternative sigma factors. Therefore, it is proposed to rename orf2 as sigY. Analysis of the phylogenetic relationship revealed that SigX from C. acetobutylicum, together with sigmaE from Streptomyces coelicolor and SigX from Bacillus subtilis, form a gram-positive cluster within the ECF subfamily and that SigY from C. acetobutylicum together with UviA from Clostridium perfringens, form a separate cluster located between the gram-positive cluster and the sporulation sigma factor sigmaH from B. subtilis.

Amino Acid Sequence↗
PubMed1999

Circadian variation of malignant ventricular arrhythmias in patients with ischemic and nonischemic heart disease after cardioverter defibrillator implantation. European 7219 Jewel Investigators.

OBJECTIVES: The purpose of this study was to examine the circadian variation of ventricular arrhythmias detected by an implantable cardioverter defibrillator in patients with and without ischemic heart disease. BACKGROUND: Previous studies have shown a circadian variation of ventricular arrhythmias, sudden death and myocardial infarction with a peak occurrence in the morning hours. The circadian pattern, which is similar for both arrhythmic and ischemic events, suggests that ischemia may play a critical role in the genesis of ventricular arrhythmias and sudden death. We hypothesized that, if ischemia plays an important role in the triggering of ventricular arrhythmias, the circadian pattern should be different in patients with ischemic heart disease compared with patients with nonischemic heart disease. METHODS: The circadian variation of ventricular arrhythmias recorded by an implantable cardioverter defibrillator was studied in 310 patients during a mean follow-up of 181 +/- 163 days. Two hundred four patients had a history of ischemic heart disease and 106 patients had nonischemic heart disease. The times of the episodes of ventricular arrhythmias were retrieved from the data log of each device during follow-up, and the circadian pattern was compared between the two groups. RESULTS: During follow-up, 1,061 episodes of ventricular arrhythmias were recorded by the device in the 310 patients. Six hundred eighty-two episodes occurred in the group of patients with ischemic heart disease and 379 occurred in the nonischemic heart disease group. The circadian variation of the episodes showed a typical pattern with a morning and afternoon peak in both groups of patients with ischemic and nonischemic heart disease, but there was no significant difference between the two groups. CONCLUSIONS: The circadian rhythm of ventricular arrhythmias in patients with ischemic heart disease is similar to patients with nonischemic heart disease, suggesting that the trigger mechanisms of the initiation of ventricular tachyarrhythmias may be similar, irrespective of the underlying heart disease.

Arrhythmias, Cardiac↗
PubMed1999

The erg-like potassium current in rat lactotrophs.

1. The ether-à-go-go-related gene (erg)-like K+ current in rat lactotrophs from primary culture was characterized and compared with that in clonal rat pituitary cells (GH3/B6). The class III antiarrhythmic E-4031 known to block specifically erg K+ channels was used to isolate the erg-like current as the E-4031-sensitive current. The experiments were performed in 150 mM K+ external solution using the patch-clamp technique. 2. The erg-like K+ current elicited with hyperpolarizing pulses negative to -100 mV consisted of a fast and a pronounced slowly deactivating current component. The contribution of the slow component to the total current amplitude was potential dependent and varied from cell to cell. At -100 mV it ranged from 50 to 85% and at -140 mV from 21 to 45%. 3. The potential-dependent channel availability curves determined with 2 s prepulses were fitted with the sum of two Boltzmann functions. The function related to the slowly deactivating component of the erg-like current was shifted by more than 40 mV to more negative membrane potentials compared with that of the fast component. 4. In contrast to that of native lactotrophs studied under identical conditions, the erg-like K+ current of GH3/B6 cells was characterized by a predominant fast deactivating current component, with similar kinetic and steady-state properties to the fast deactivating current component of native lactotrophs. 5. Thyrotrophin-releasing hormone reduced the erg-like current in native lactotrophs via an intracellular signal cascade which seemed to involve a pathway independent from protein kinase A and protein kinase C. 6. RT-PCR studies on cytoplasm from single lactotrophs revealed the presence of mRNA of the rat homologue of the human ether-à-go-go-related gene HERG (r-erg1) as well as mRNA of the two other cloned r-erg cDNAs (r-erg2 and r-erg3) in different combinations. In GH3/B6 cells, only the transcripts of r-erg1 and r-erg2 were found.

Animals↗
PubMed1999

Long-term follow-up and outcome in patients treated for spinal dural arteriovenous fistula.

Clinical outcome was examined in 21 patients treated for spinal dural arteriovenous fistula after 5-50 months. We compared the neurological condition (motor function, pain, sensory disturbance, vegetative dysfunction) and Barthel index before and after fistula occlusion. Neurological impairment was assessed as improved, unchanged, or deteriorated. All patients initially showed paraparesis of varying degree, and a sensory loss with a defined level in 81% before treatment. The greatest postoperative change that we measured was in motor activity (67% improved), and the most important deterioration was in male potency (28% deteriorated). We observed unchanged or absent symptoms in pain in 71% of our patients. We were thus able not only to stop but even to reverse the progression of symptoms and the degree of disability. On average, neurological symptoms stabilized within 1 year. The results of this study confirm that spinal dural arteriovenous fistula should be treated as early as possible after diagnosis.

Adult↗