Biomedical subjects
Publications and source records attributed to A Friedrich.
UNLABELLED: MAGOS is a web server allowing automated protein modelling coupled to the creation of a hierarchical and annotated multiple alignment of complete sequences. MAGOS is designed for an interactive approach of structural information within the framework of the evolutionary relevance of mined and predicted sequence information. AVAILABILITY: The web server is freely available at http://pig-pbil.ibcp.fr/magos.
The compressibilities of the nitridosilicate SrYb[Si(4)N(7)] and the oxonitridoaluminosilicates MYb[Si(4-x)Al(x)O(x)N(7-x)] (x = 2; M = Sr, Ba) were investigated by in situ high-pressure X-ray powder diffraction. Pressures up to 42 GPa were generated using the diamond-anvil cell technique. The title compounds are structurally stable to the highest pressure obtained. A fit of a third-order Birch-Murnaghan equation-of-state to the p-V data results in V(0) = 302.91 (6) A(3), B(0) = 176 (2) GPa and B' = 4.4 (2) for SrYb[Si(4)N(7)]; V(0) = 310.4 (1) A(3), B(0) = 161 (2) GPa and B' = 4.6 (2) for SrYb[Si(4-x)Al(x)O(x)N(7-x)]; and V(0) = 317.3 (5) A(3), B(0) = 168 (2) GPa and B' = 4.7 (2) for BaYb[Si(4-x)Al(x)O(x)N(7-x)]. While the linear compressibilities of the a and c axes of BaYb[Si(4-x)Al(x)O(x)N(7-x)] are very similar up to 30 GPa, distinct differences were observed for SrYb[Si(4)N(7)] and SrYb[Si(4-x)Al(x)O(x)N(7-x)], with the c axis being the most compressible axis. In all of the investigated compounds the bulk compressibility is dominated by the compression behaviour of the tetrahedral network, while the size of the substituted cation plays a minor role.
Current DNA amplification-based typing methods for bacterial pathogens often lack interlaboratory reproducibility. In this international study, DNA sequence-based typing of the Staphylococcus aureus protein A gene (spa, 110 to 422 bp) showed 100% intra- and interlaboratory reproducibility without extensive harmonization of protocols for 30 blind-coded S. aureus DNA samples sent to 10 laboratories. Specialized software for automated sequence analysis ensured a common typing nomenclature.
BACKGROUND: The molecular mechanism of increased background inward rectifier current (IK1) in atrial fibrillation (AF) is not fully understood. We tested whether constitutively active acetylcholine (ACh)-activated I(K,ACh) contributes to enhanced basal conductance in chronic AF (cAF). METHODS AND RESULTS: Whole-cell and single-channel currents were measured with standard voltage-clamp techniques in atrial myocytes from patients with sinus rhythm (SR) and cAF. The selective I(K,ACh) blocker tertiapin was used for inhibition of I(K,ACh). Whole-cell basal current was larger in cAF than in SR, whereas carbachol (CCh)-activated I(K,ACh) was lower in cAF than in SR. Tertiapin (0.1 to 100 nmol/L) reduced I(K,ACh) in a concentration-dependent manner with greater potency in cAF than in SR (-logIC50: 9.1 versus 8.2; P<0.05). Basal current contained a tertiapin-sensitive component that was larger in cAF than in SR (tertiapin [10 nmol/L]-sensitive current at -100 mV: cAF, -6.7+/-1.2 pA/pF, n=16/5 [myocytes/patients] versus SR, -1.7+/-0.5 pA/pF, n=24/8), suggesting contribution of constitutively active I(K,ACh) to basal current. In single-channel recordings, constitutively active I(K,ACh) was prominent in cAF but not in SR (channel open probability: cAF, 5.4+/-0.7%, n=19/9 versus SR, 0.1+/-0.05%, n=16/9; P<0.05). Moreover, IK1 channel open probability was higher in cAF than in SR (13.4+/-0.4%, n=19/9 versus 11.4+/-0.7%, n=16/9; P<0.05) without changes in other channel characteristics. CONCLUSIONS: Our results demonstrate that larger basal inward rectifier K+ current in cAF consists of increased IK1 activity and constitutively active I(K,ACh). Blockade of I(K,ACh) may represent a new therapeutic target in AF.
We present a two-frequency method to investigate lateral interaction components (liERGs) in the human electroretinogram. Adjacent half cycles of sinusoidal gratings were modulated sinusoidally with different temporal frequencies f1 and f2. The liERGs were defined by the Fourier components at the intermodulation frequencies /f1 - f2/ and f1 + f2 which indicate nonlinear interactions between the half cycles. Significant liERGs were found in all subjects with a monotonic increase of the liERG magnitude in the spatial frequency range from f(s)=0.07 to 2.4 cpd. When /f1 - f2/ was below 5 Hz, liERGs were masked by noise intrusions. In a control experiment we demonstrated that the liERGs were not evoked by stray light artifacts. The liERGs may help to further differentiate the responses that are evoked by patterned stimuli within the retina.
The burden of insufficiently treated arterial hypertension is still underestimated. In addition to pharmacological therapy, patient training is a valuable therapeutic option. During 1998-1999, the Institute for Preventive Medicine conducted an intensive training programme in cooperation with regional practitioners. The goal of this programme was to educate patients about their disease and motivate them to comply with the therapy. To evaluate the effectivity of this programme, 126 patients with arterial hypertension were trained. They received eight training sessions of 90 min each. In 90 patients blood pressure measurements before and 6 months after training were available. In addition, data concerning health status and lifestyle risk factors were analysed with standardised questionnaires. There was a marked reduction in blood pressure after 6 months (152+/-6/89+/-10 vs. 145+/-12/85+/-8 mmHg, P<0.001). In parallel, mean body weight declined by 0.9 +/- 2.9 kg (P<0.001) and body mass index (BMI) by 0.33+/-1.04 kg/m2 (P<0.001). Further analysis revealed that weight loss was more marked in obese patients (P< 0.01) than in lean subjects. Similarly, the decline of blood pressure was also greater in obese patients, but did not reach statistical significance. The activity score for physical exercise increased overall from 2.1+/-0.4 to 2.8+/-3.1 h/week (P<0.01). Moreover, knowledge about hypertension increased as well (P<0.01). Of all the quality life measurements, the vitality index improved from 53+/-19 to 59+/-19 (P<0.05) according to the patients' self-estimation. In conclusion, training of hypertensive patients has a profound effect on blood pressure control. It motivates patients to change lifestyle risk factors, namely to lose weight, and increases the patients' physical activity level, thereby decreasing the patients' blood pressure. Thus, intensive training programmes are effective and should be used on a widespread basis.
Squamous cell carcinomas account for more than 80 % of esophageal malignancies in Germany. Alcohol and tobacco smoke are two of the most important risk factors. In superficial esophageal squamous cell carcinoma, endoscopic mucosal resection (EMR) is a very useful and effective treatment modality. However, in patients with submucosal esophageal cancer, radical esophageal resection is regarded as the gold standard for treatment at present. We report the case of a 71-year-old female patient with alcohol-induced liver cirrhosis with esophageal varices and a - therefore inoperable - early esophageal squamous cell carcinoma. Photodynamic therapy (PDT) using 5-aminolevulinic acid (5-ALA) seemed not to be an effective treatment modality due to its limited penetration depth (< 2 mm) and the liver toxicity of 5-ALA. PDT using Photofrin(R) with a higher penetration depth seemed to be associated with a high risk of bleeding due to the esophageal varices. Furthermore, this sensitizer is associated with a high rate of strictures and a long-lasting skin sensitivity. In contrast, arguments against an endoscopic mucosal resection (EMR) were endosonographically suspected submucosal tumor growth and a high risk of bleeding. Nevertheless, with respect to the lack alternatives we decided to perform an EMR after ligation of esophageal varices. The tumor could be resected in sano without major bleeding complication. Histology demonstrated a carcinoma in situ without submucosal invasion. After 3 months a second EMR was necessary due to recurrence. Meanwhile after a follow-up period of 18 months only low grade intraepithelial neoplasia without macroscopically suspicious lesions was observed.
Self incompatibility (SI) in Phalaris coerulescens is gametophytically determined by two unlinked multi allelic loci (S and Z). Neither the S nor Z genes have yet been cloned. As part of a map-based cloning strategy, high-resolution maps of the S and Z regions were generated from distorted segregating populations using RFLP probes from wheat, barley, oat, and Phalaris. The S locus was delimited to 0.26 cM with two boundary markers (Xwg811 and Xpsr168) and cosegregated with Xbm2 and Xbcd762. Xbcd266 was the closest marker linked to Z (0.9 cM). A high level of colinearity in the S and Z regions was found in both self-incompatible and -compatible species. The S locus was localized to the subcentromere region of chromosome 1 and the Z locus to the long arm end of chromosome 2. Several rice BAC clones orthologous to the S and Z locus regions were identified. This opens the possibility of using the rice genome sequence data to generate more closely linked markers and identify SI candidate genes. These results add further support to the conservation of gene order in the S and Z regions of the grass genomes.
The transcription factor CREB (cAMP response element binding protein) is required for the switch from short-term to long-term synaptic plasticity and from short-term to long-term memory. Its activity is regulated by the cAMP-dependent signalling cascade, which has been shown to play a crucial role in the honeybee's long-term memory formation. To elucidate the role of the CREB in honeybee memory formation we analysed a CREB-homologous gene, AmCREB, which is expressed as several transcripts in the honeybee brain. Eight transcripts have been identified (AmCREB 1-8) that are generated by alternate splicing. One antibody generated against a subset of these variants reveals a cytosolic localization in the mushroom body alpha-lobes, the glomeruli of the antennal lobes, the protocerebral lobes, the central complex and in the optical lobes.
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PROBLEM: Multifocal electroretinogram recordings (mfERG) can be used to detect a local dysfunction of the retina. In this study we tested both the intrasessional and inter-sessional reproducibility of mfERG amplitudes. METHODS: MfERGs from 6 eyes of 6 normal subjects were recorded on two different days using DTL electrodes. The relative coefficient of variation ( RCV) was used to quantify the amplitude reproducibility. We tested the effect of (a) session (inter- vs. intrasessional), (b) recording duration (7.3 vs. 3.6 min), (c) trace type (hexagon traces vs. ring averages), and (d) amplitude definition (peak-trough analysis vs. scalar product) on RCV. RESULTS: RCV was 6.5+/-0.4% (Mean+/-SEM, n=96) when averaged across all recording conditions and all subjects. The ANOVA showed a significant difference ( p=0.018) between hexagon traces and ring averages. Another significant effect ( p=0.016) occurred for the interaction of (a) and (b). CONCLUSION: MfERGs can be recorded with a high degree of reproducibility even for short recording durations and single hexagon traces. As the factor (a) did not show a significant effect, the new placement of the DTL electrode in the second session does not necessarily increase the retest variability compared to a second recording within the same session.
The structural behaviour of both low-temperature beta- and high-temperature alpha-Ba(OD)(2), barium dihydroxide-d, was investigated at temperatures between 10 and 552 K by neutron powder diffraction. While the beta phase (P2(1)/n) remains stable to the lowest temperature investigated, the quenchable alpha phase (Pnma) shows a reversible orthorhombic-to-monoclinic phase transition between 100 and 150 K. The structure of the new alpha(m) phase (P2(1)/n) is quite similar to that of the alpha phase. This behaviour is unusual as a metastable phase transforms to another metastable phase. The Pnma <--> P2(1)/n low-temperature phase transition is driven by an order-disorder mechanism, mainly caused by one of the D atoms, which is disordered on positions off the mirror plane, mimicking a special position on the mirror plane in the orthorhombic phase. Refinements of the alpha phase above the phase transition indicate this disorder across the mirror plane through a conspicuously high isotropic displacement parameter if compared to the other D atoms. At low temperature the energy of the vibration is lowered and the D atom is frozen at a general position in a correlated way, thus violating the mirror plane and reducing the space-group symmetry.
The present study was undertaken to elucidate the functional characteristics of choline uptake and deduce the relationship between choline uptake and the expression of organic cation transporters in the rat brain microvessel endothelial cell line RBE4. Confluent RBE4 cells were found to express a high affinity choline uptake system. The system is Na(+)-independent and shows a Michaelis-Menten constant of approx. 20 microM for choline. The choline analogue hemicholinium-3 inhibits choline uptake in these cells with an inhibition constant of approx. 50 microM. The uptake system is also susceptible for inhibition by various organic cations, including 1-methyl-4-phenylpyridinium, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, clonidine, procainamide, and tetramethylammonium. The prototypical organic cation tetraethylammonium shows very little affinity for the choline uptake system in these cells. The inhibition of choline uptake by hemicholinium-3 is competitive. Northern analysis and RT-PCR show that these cells do not express the organic cation transporters OCT2 and OCT3. These cells do express, however, low levels of OCT1, but the functional characteristics of choline uptake in these cells are very different from the known properties of choline uptake via OCT1. The Na(+)-coupled high affinity choline transporter CHT1 is not expressed in these cells as evidenced by RT-PCR. This corroborates the Na(+)-independent nature of choline uptake in these cells. It is concluded that RBE4 cells express an organic cation transporter that is responsible for choline uptake in these cells and that this transporter is not identical to any of the organic cation transporters thus far identified at the molecular level in mammalian cells.
Various radiotracers based on uracil nucleosides (e.g. [124I]2'-fluoro-2'-deoxy-5-iodo-1-beta-D-arabinofuranosyluracil, [124I]FIAU) and acycloguanosine derivatives (e.g. [18F]9-[(3-fluoro-1-hydroxy-2-propoxy) methyl] guanine, [18F]FHPG) have been proposed for the non-invasive imaging of herpes simplex virus type 1 thymidine kinase (HSV1-tk) reporter gene expression. However, these radiotracers have been evaluated in different in vitro and in vivo models, precluding a direct comparison. Therefore, we directly compared [18F]FHPG and radioiodinated FIAU to assess their potential for PET imaging of transgene expression. The uptake of [125I]FIAU, [18F]FHPG and [3H]acyclovir was determined in vitro using four different HSV1-tk expressing cell lines and their respective negative controls. The in vitro tracer uptake was generally low in non-transduced parental cell lines. In HSV1-tk expressing cells, [3H]acyclovir showed approximately a twofold higher tracer accumulation, the [18F]FHPG uptake increased by about sixfold and the [125I]FIAU accumulation increased by about 28-fold after 120-min incubation of T1115 human glioblastoma cells. Similar results were found in the other cell lines. In addition, biodistribution and positron emission tomography (PET) studies with [18F]FHPG and [124/125I]FIAU were carried out in tumour-bearing BALB/c mice. Significantly higher specific accumulation of radioactivity was found for [125I]FIAU compared with [18F]FHPG. The ratio of specific tracer accumulation between [125I]FIAU and [18F]FHPG increased from 21 (30 min p.i.) to 119 (4 h p.i.). PET imaging, using [124I]FIAU, clearly visualised and delineated HSV1-tk expressing tumours, whereas only a negligible uptake of [18F]FHPG was observed. This study demonstrated that in vitro and in vivo, the radioiodinated uracil nucleoside FIAU has a significantly higher specific accumulation than the acycloguanosine derivative [18F]FHPG. This suggests that [124I]FIAU should be the preferred reporter probe for PET imaging of HSV1-tk gene expression. Thus, further attempts to develop suitable PET tracers for the assessment of HSV1-tk gene expression should also focus on 18F-labelled uracil derivatives.
The mesophile Acinetobacter sp. strain BD413 and the extreme thermophile Thermus thermophilus HB27 display high frequencies of natural transformation. In this study we identified and characterized a novel competence gene in Acinetobacter sp. strain BD413, comA, whose product displays significant similarities to the competence proteins ComA and ComEC in Neisseria and Bacillus species. Transcription of comA correlated with growth phase-dependent transcriptional regulation of the recently identified pilin-like factors of the transformation machinery. This finding strongly suggests that comA is part of a competence regulon. Examination of the genome sequence of T. thermophilus HB27 led to detection of a comA/comEC-like open reading frame (ORF) which is flanked by an ORF whose product shows significant similarities to the Bacillus subtilis competence protein ComEA. To examine whether these two ORFs, designated comEC and comEA, are implicated in natural transformation of T. thermophilus HB27, both were disrupted by using a thermostable kanamycin resistance marker. Natural transformation in comEC mutants was reduced 1,000-fold, whereas in comEA mutants the natural transformation phenotype was completely eliminated. These results strongly suggest that both genes, comEC and comEA, are required for natural transformation in T. thermophilus HB27. Several transmembrane alpha-helices are predicted based on the amino acid sequences of ComA in Acinetobacter sp. strain BD413 and ComEC in T. thermophilus HB27, which suggests that ComA and ComEC are located in the inner membrane and function in DNA transport through the cytoplasmic membrane.
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BACKGROUND AND OBJECTIVE: The burden of insufficiently treated arterial hypertension is still underestimated. During 1998 to 1999 we conducted an intensive training program in cooperation with regional practitioners. The aim of this program was to educate the patients about their disease and motivate them to comply with therapy. The effectivity of this program yet needs to be evaluated. PATIENTS AND METHODS: 146 patients (mean age 62 years; 57 male, 89 female) with arterial hypertension were trained. They received 8 training units of 90 min each. Before training and 6 months after training data concerning health status and life style risk factors were assessed with questionnaires. RESULTS: There was a marked reduction in blood pressure after 6 months (152/89 mmHg vs 145/85 mmHg, p < 0.001). The mean body weight also declined on the average by 0.9 kg (p < 0.001). Physical exercise spent per week increased from mean 2.0 to 2.8 hours (p < 0.01). Moreover, knowledge about hypertension increased (p < 0.001). The established questionnaire SF-36 revealed a better score for vitality (p < 0.05) six months after therapy than before. CONCLUSION: Our intensive training program of patients with arterial hypertension has profound effects on their systolic and diastolic blood pressure. It also motivates patients to change life style. Our data suggest that intensive training programs should be developed on a widespread basis.
Predisposing factors, clinical characteristics, and antimicrobial treatment of 37 hematology patients with Stenotrophomonas maltophilia bacteremia who were seen at the department of hematology of the University La Sapienza (Rome) from 1987 to 1996 were evaluated. The results were compared with a control group of patients with Pseudomonas aeruginosa bacteremia. Profound neutropenia was more prolonged in the S. maltophilia group (P=.025), severe cellulitis occurred only in S. maltophilia-infected patients (11 [30%]; P=.0002), and the bacteremia presented as breakthrough infection in 56% of the cases due to S. maltophilia (vs. only 24% of those due to P. aeruginosa; P=.002). Acute mortality rates associated with S. maltophilia and P. aeruginosa bacteremia were 24% and 21%, respectively. In both groups, profound neutropenia and hypotension at the onset of bacteremia, duration of profound neutropenia during bacteremia, severity-of-illness score > or =4, and inappropriate antibacterial treatment were factors significantly associated with death. Most S. maltophilia isolates were resistant to aminoglycosides, beta-lactams, and ciprofloxacin. Cotrimoxazole and ticarcillin-clavulanic acid showed borderline activity. Prompt administration of in vitro-active antibiotics may improve the prognosis of S. maltophilia bacteremia, especially for immunocompromised patients, and novel drug combinations are needed for the treatment of severe infections.