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Henrik Folker,Anna Paldam Folker INTRODUCTION:WHO-5 is a questionnaire for self-administration developed to evaluate well-being and quality of life. It is documented that a score of <50 is often related to a depressive state. In this investigation it is used to evaluate the general quality of life and changes here of during treatm... ( view more )ent of patients from all diagnostic groups of psychiatry. MATERIALS AND METHODS: The questionnaire was administered at admission and discharge to 377 patients in psychiatric wards. Another questionnaire MDI (major depression inventory) was used as a supplement. RESULTS: By using the WHO-5 questionnaire in the psychosis group a progress in quality of life from 32 to 58 was obtained. In the affective group the progress was from 20 to 52. The method had a high sensitivity in its ability to discover the patients who were given a discharge diagnosis of depression. Specificity was lower. WHO-5 could be used to measure the effect of treatment with different psychopharmacological treatments. CONCLUSION: WHO-5 can be used as a general measure of well-being and quality of life and it is demonstrated how different treatments can be evaluated. According to a philosophical analysis of the concept of quality of life, WHO-5 mainly covers the hedonistic aspects. The WHO-5 questionnaire is quite simple and most patients understand the concept immediately. It takes only a few minutes to answer the questionnaire. ( view less ) R H Folmer,P J Folkers,A Kaan,A J Jonker,J M Aelen,R N Konings,C W Hilbers Nuclear magnetic resonance spectroscopy was employed to study the single-stranded DNA binding protein encoded by the filamentous Pseudomonas bacteriophage Pf3. The protein is 78 amino acids long and occurs in solution predominantly as a homodimer with a molecular mass of 18 kDa. Sequence-specific 1... ( view more )H and 15N resonance assignments have been obtained using homo- and heteronuclear two- and three-dimensional experiments. The secondary structure of the protein monomer was determined from a qualitative interpretation of nuclear Overhauser enhancement spectra and amide exchange data. It consists of a five-stranded antiparallel beta-sheet and three beta-hairpins. Problems caused by the protein's tendency to aggregate at concentrations needed for NMR spectroscopy were largely overcome by designing a mutant (Phe36-->His) which exhibits significantly improved solubility characteristics over the wild-type protein. It is shown that this mutation only locally affects the structure of the protein; the chemical shifts of the wild-type and mutant species differ only for a few residues near the site of the mutation, and the secondary structures of the proteins are identical. The secondary structure of the Pf3 single-stranded DNA binding protein is compared to that of the Ff gene V protein, the only single-stranded DNA binding protein for which the complete three-dimensional structure is known to date [Folkers, P. J. M., Nilges, M., Folmer, R. H. A., Konings, R. N. H. & Hilbers, C. W. (1994) J. Mol. Biol. 236, 229-246; Skinner, M. M., Zhang, H., Leschnitzer, D. H., Guan, Y., Bellamy, H., Sweet, R. M., Gray, C. W., Konings, R. N. H., Wang, A. H.-J. & Terwilliger, T. C. (1994) Proc. Natl Acad. Sci. USA 91, 2071-2075]. It is found that the secondary structures of the two proteins are very similar which supports the hypothesis that a five-stranded antiparallel beta-sheet with protruding beta-hairpins is a common motif in a certain class of single-stranded DNA binding proteins. In addition, the sequence and folding predicted earlier for the DNA binding wing in the single-stranded DNA binding protein of phage Pf3 [de Jong, E. A. M., van Duynhoven, J. P. M., Harmsen, B. J. M., Tesser, G. I., Konings, R. N. H. & Hilbers, C. W. (1989) J. Mol. Biol. 206, 133-156] is borne out by the present study. It closely resembles that in the single-stranded DNA binding protein of phage Ff, which may indicate that such a wing is a recurrent motif as well. ( view less ) P J Folkers,J P van Duynhoven,A J Jonker,B J Harmsen,R N Konings,C W Hilbers Sequence-specific 1H-NMR assignments are reported for the Tyr41----His (Y41H) mutant of the single-stranded DNA binding protein, encoded by gene V of the filamentous bacteriophage M13 (GVP). The mutant protein was chosen for this purpose because it exhibits significantly improved solubility charact... ( view more )eristics over wild-type GVP [Folkers et al. (1991) Eur. J. Biochem. 200, 139-148]. The secondary structure elements present in the protein are deduced from a qualitative interpretation of the nuclear Overhauser enhancement spectra and amide exchange data. The protein is entirely composed of antiparallel beta-structure. It is shown that identical structural elements are present in wild-type GVP. Previously, we have demonstrated that the secondary structure of the beta-loop, encompassing residues 13-31 which is present in GVP in solution, deviates from that proposed for the same amino acid sequence on the basis of X-ray diffraction data [van Duynhoven et al. (1990) FEBS Lett. 261, 1-4]. Now that we have arrived at a complete description of the secondary structure of the protein in solution, other deviations with respect to the crystallographically determined structure became apparent as well. The N-terminal part of the protein is, in solution, part of a triple-stranded beta-sheet while, in the crystal, it is an extended strand pointing away from the bulk of the protein dimer. One of the antiparallel beta-sheets in the protein which had been designated earlier as the complex loop has, in the solution structure, a different pairwise arrangement of the residues in its respective beta-ladders. Residues 30 and 48 are opposite to one another in the solution structure while in the crystal structure residues 32 and 48 are paired. A similar observation is made for the so-called dyad domain of the protein of which the beta-sheet in the solution structure is shifted by one residue with respect to that of the crystal structure. ( view less ) K Folkers,P Langsjoen,R Willis,P Richardson,L J Xia,C Q Ye,H Tamagawa Lovastatin is clinically used to treat patients with hypercholesterolemia and successfully lowers cholesterol levels. The mechanism of action of lovastatin is inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, an enzyme involved in the biosynthesis of cholesterol from acetyl-CoA. Inhibi... ( view more )tion of this enzyme could also inhibit the intrinsic biosynthesis of coenzyme Q10 (CoQ10), but there have not been definitive data on whether lovastatin reduces levels of CoQ10 as it does cholesterol. The clinical use of lovastatin is to reduce a risk of cardiac disease, and if lovastatin were to reduce levels of CoQ10, this reduction would constitute a new risk of cardiac disease, since it is established that CoQ10 is indispensable for cardiac function. We have conducted three related protocols to determine whether lovastatin does indeed inhibit the biosynthesis of CoQ10. One protocol was done on rats, and is reported in the preceding paper [Willis, R. A., Folkers, K., Tucker, J. L., Ye, C.-Q., Xia, L.-J. & Tamagawa, H. (1990) Proc. Natl. Acad. Sci. USA 87, 8928-8930]. The other two protocols are reported here. One involved patients in a hospital, and the other involved a volunteer who permitted extraordinary monitoring of CoQ10 and cholesterol levels and cardiac function. All data from the three protocols revealed that lovastatin does indeed lower levels of CoQ10. The five hospitalized patients, 43-72 years old, revealed increased cardiac disease from lovastatin, which was life-threatening for patients having class IV cardiomyopathy before lovastatin or after taking lovastatin. Oral administration of CoQ10 increased blood levels of CoQ10 and was generally accompanied by an improvement in cardiac function. Although a successful drug, lovastatin does have side effects, particularly including liver dysfunction, which presumably can be caused by the lovastatin-induced deficiency of CoQ10. ( view less ) M Sheldon,W P Whitely,B Folker,A W Hafner,W Gaylin This case study and three commentaries involve a contemporary researcher pondering the moral implications of using Nazi experimental data related to his work. How should Nazi data be regarded? Is it tainted information, or morally neutral? Should researchers today treat this data differently tha... ( view more )n more conventionally gathered information? Mark Sheldon and William Whitely cite Kristine Moe's four conditions that, if met, may justify the use of Nazi data. They conclude that, while researchers may be obliged to use the data if it can preserve life, by doing so they may be desecrating the memory of Nazi victims unless they can continually and creatively sustain a sense of condemnation. Brian Folker and Arthur Hafner reject the use of Nazi data, but conclude that each researcher must decide out of a concern for him- or herself as a moral being. Willard Gaylin argues that to use Nazi data is to legitimatize it and to become an accomplice. ( view less ) Anna Paldam Folker,Peter Sandøe This article deals with scientific advice to the public where the relevant science is subject to public attention and uncertainty of knowledge. It focuses on a tension in the management and presentation of scientific uncertainty between the uncertain nature of science and the expectation that scien... ( view more )tific advisers will provide clear public guidance. In the first part of the paper the tension is illustrated by the presentation of results from a recent interview study with nutrition scientists in Denmark. According to the study, nutrition scientists feel their roles as ''public advisers'' and ''scientists'' differ in that the former involves an expectation that they will provide unambiguous advice of the kind that might relegate scientific uncertainty to the background. In the second, more general, part of the paper we provide a normative analysis of different strategies of dealing with the tension. The analysis is structured around the extremes of either total concealment or full openness regarding scientific uncertainty. The result of analysis is that scientific advisers should not simply ''feed'' scientific conclusions to the public. They should rather attempt to promote the ability and willingness of the public to assess and scrutinize scientific knowledge by displaying uncertainties in the scientific basis of advice. On the other hand, scientific advisers must accommodate the public's need for guidance. Such guidance should be restricted by careful consideration of what it is relevant for the public to know in order to evaluate scientific advice in practical terms. ( view less ) Steffi F Dreha-Kulaczewski,Peter Dechent,Jürgen Finsterbusch,Knut Brockmann,Jutta Gärtner,Jens Frahm,Folker A Hanefeld The neuropathology of vanishing white matter (VWM) disease is characterized by a loss of white matter (WM). Although recent histopathological studies suggest a primary glial dysfunction, the purpose of this work was to assess the extent of axonal involvement in VWM using long-term follow-up proton ... ( view more )MR spectroscopy. White and gray matter of nine children with genetically proven VWM and late infancy/early childhood onset were investigated with short-echo time, single-voxel proton MR spectroscopy over up to 8 years starting as early as less than 2 years after the onset of symptoms (5 patients). Total N-acetyl-aspartate (-51% from normal control), creatine and phosphocreatine (-47%), and myo-inositol (-49%) were reduced in WM at early disease stages. Choline-containing compounds were less severely decreased (-31%). Follow-up investigations revealed progressive reduction of all metabolites in WM. In gray matter, no distinct changes were detected at early stages. Later total N-acetyl-aspartate decreased slightly (-22%). Assuming the metabolite alterations to primarily reflect changes in cellular composition, the observed pattern indicates early axonal involvement or loss as well as relatively enhanced turnover of myelin. These early stages are followed by a complete cellular loss in cerebral WM. ( view less ) Devashish Das,Konstantinos Tripsianes,Nicolaas G J Jaspers,Jan H J Hoeijmakers,Robert Kaptein,Rolf Boelens,Gert E Folkers The human XPF-ERCC1 protein complex plays an essential role in nucleotide excision repair by catalysing positioned nicking of a DNA strand at the 5' side of the damage. We have recently solved the structure of the heterodimeric complex of the C-terminal domains of XPF and ERCC1 (Tripsianes et al., ... ( view more )Structure 2005;13:1849-1858). We found that this complex comprises a pseudo twofold symmetry axis and that the helix-hairpin-helix motif of ERCC1 is required for DNA binding, whereas the corresponding domain of XPF is functioning as a scaffold for complex formation with ERCC1. Despite the functional importance of heterodimerization, the C-terminal domain of XPF can also form homodimers in vitro. We here compare the stabilities of homodimeric and heterodimeric complexes of the C-terminal domains of XPF and ERCC1. The higher stability of the XPF HhH complexes under various experimental conditions, determined using CD and NMR spectroscopy and mass spectrometry, is well explained by the structural differences that exist between the HhH domains of the two complexes. The XPF HhH homodimer has a larger interaction interface, aromatic stacking interactions, and additional hydrogen bond contacts as compared to the XPF/ERCC1 HhH complex, which accounts for its higher stability. ( view less ) Karl-Heinz Gartemann,Birte Abt,Thomas Bekel,Annette Burger,Jutta Engemann,Monika Flügel,Lars Gaigalat,Alexander Goesmann,Ines Gräfen,Jörn Kalinowski,Olaf Kaup,Oliver Kirchner,Lutz Krause,Burkhard Linke,Alice McHardy,Folker Meyer,Sandra Pohle,Christian Rückert,Susanne Schneiker,Eva-Maria Zellermann,Alfred Pühler,Rudolf Eichenlaub,Olaf Kaiser,Daniela Bartels Clavibacter michiganensis subsp. michiganensis is a plant-pathogenic actinomycete that causes bacterial wilt and canker of tomato. The nucleotide sequence of the genome of strain NCPPB382 was determined. The chromosome is circular, consists of 3.298 Mb, and has a high G+C content (72.6%). Annotatio... ( view more )n revealed 3,080 putative protein-encoding sequences; only 26 pseudogenes were detected. Two rrn operons, 45 tRNAs, and three small stable RNA genes were found. The two circular plasmids, pCM1 (27.4 kbp) and pCM2 (70.0 kbp), which carry pathogenicity genes and thus are essential for virulence, have lower G+C contents (66.5 and 67.6%, respectively). In contrast to the genome of the closely related organism Clavibacter michiganensis subsp. sepedonicus, the genome of C. michiganensis subsp. michiganensis lacks complete insertion elements and transposons. The 129-kb chp/tomA region with a low G+C content near the chromosomal origin of replication was shown to be necessary for pathogenicity. This region contains numerous genes encoding proteins involved in uptake and metabolism of sugars and several serine proteases. There is evidence that single genes located in this region, especially genes encoding serine proteases, are required for efficient colonization of the host. Although C. michiganensis subsp. michiganensis grows mainly in the xylem of tomato plants, no evidence for pronounced genome reduction was found. C. michiganensis subsp. michiganensis seems to have as many transporters and regulators as typical soil-inhabiting bacteria. However, the apparent lack of a sulfate reduction pathway, which makes C. michiganensis subsp. michiganensis dependent on reduced sulfur compounds for growth, is probably the reason for the poor survival of C. michiganensis subsp. michiganensis in soil. ( view less ) Roman Metzger,Udo Rolle,Henning C Fiegel,Folker E Franke,Karsten Muenstedt,Holger Till The molecular mechanisms underlying the regulation of vas deferens (VD) motility and semen emission are still poorly understood. Interstitial cells of Cajal (ICC), which harbour the c-kit receptor (CD117), provide the basis of coordinated gut motility. We investigated whether c-kit receptor-positiv... ( view more )e cells also exist in the normal human VD. Enzyme and fluorescence immunohistochemical techniques were applied on serial sections of human proximal, middle, and distal VD segments (n=49) employing 13 different monoclonal and polyclonal antibodies recognizing the c-kit receptor. The c-kit receptor was detected in either round- or spindle-shaped cells. On account of their antigenic profile, the round- and oval-shaped c-kit receptor-positive cells were identified as mast cells (MC) occurring in all layers of the VD except the epithelium. In contrast, two distinct populations of exclusively c-kit receptor-positive spindle-shaped cells were found within the lamina propria and, rarely, in the inner and outer smooth muscle layers, as well as within the epithelium. Different shaped c-kit receptor-positive MC and IC were present in all layers of the human VD. Our findings demonstrate the presence of different c-kit receptor-positive cells also in the human VD. Their rather ubiquitous distribution within the lamina propria and muscle layers suggests that IC and MC may modulate the neuromuscular transmission and the propagation of electrical signals in multiple systems involved in the draining of fluids. The importance of the c-kit receptor-positive interepithelial cells remains unclear. ( view less ) Stefan M Sievert,Kathleen M Scott,Martin G Klotz,Patrick S G Chain,Loren J Hauser,James Hemp,Michael Hügler,Miriam Land,Alla Lapidus,Frank W Larimer,Susan Lucas,Stephanie A Malfatti,Folker Meyer,Ian T Paulsen,Qinghu Ren,Jörg Simon,USF Genomics Class  Sulfur-oxidizing epsilonproteobacteria are common in a variety of sulfidogenic environments. These autotrophic and mixotrophic sulfur-oxidizing bacteria are believed to contribute substantially to the oxidative portion of the global sulfur cycle. In order to better understand the ecology and roles ... ( view more )of sulfur-oxidizing epsilonproteobacteria, in particular those of the widespread genus Sulfurimonas, in biogeochemical cycles, the genome of Sulfurimonas denitrificans DSM1251 was sequenced. This genome has many features, including a larger size (2.2 Mbp), that suggest a greater degree of metabolic versatility or responsiveness to the environment than seen for most of the other sequenced epsilonproteobacteria. A branched electron transport chain is apparent, with genes encoding complexes for the oxidation of hydrogen, reduced sulfur compounds, and formate and the reduction of nitrate and oxygen. Genes are present for a complete, autotrophic reductive citric acid cycle. Many genes are present that could facilitate growth in the spatially and temporally heterogeneous sediment habitat from where Sulfurimonas denitrificans was originally isolated. Many resistance-nodulation-development family transporter genes (10 total) are present; of these, several are predicted to encode heavy metal efflux transporters. An elaborate arsenal of sensory and regulatory protein-encoding genes is in place, as are genes necessary to prevent and respond to oxidative stress. ( view less ) Bernd Krone,Daniela Pohl,Kevin Rostasy,Elke Kahler,Edgar Brunner,Frank Oeffner,John M Grange,Jutta Gärtner,Folker Hanefeld Environmental factors, in particular infections, have been linked with the risk of developing multiple sclerosis (MS). The association of Epstein-Barr virus infection with childhood onset of MS has been recently recognized. As other infections characteristically experienced during childhood have no... ( view more )t yet been studied in larger cohorts of paediatric MS, we conducted a study on 152 German children with MS (age at onset <16 years) and matched controls in the hope of gaining evidence for their possible aetiological role in MS. Patterns of antibody responses were determined to a range of infections which, in prior studies principally on adult patients, had revealed possible associations with MS. In this study on children the serology of several infections showed associations with MS. In the exceptional case of Chlamydia pneumoniae there was a significantly higher prevalence of IgM antibody but, more typically, as in the case of influenza A, measles, parainfluenza 2, varicella/zoster viruses and particularly to the herpes simplex virus type 2 (HSV-2) lysate antigen, there were significantly higher concentrations of IgG antibody. Additional investigations, however, make it highly unlikely that a relevant number of children have experienced infections with HSV-2. In general this study supports and emphasizes a complex infectious and immunologic background of MS. ( view less ) Anna Paldam Folker,Hanne Andersen,Peter Sandøe This paper focuses on implicit normative considerations underlying scientific advice -- those normative questions, decisions, or issues that scientific advisers and the general public are not fully aware of but that nevertheless have implications for the character of the advice given. Using nutriti... ( view more )onal science as an example, we identify three such implicit normative issues. The first concerns the aim of scientific advice: whether it is about avoiding harm or promoting good. The second concerns the intended beneficiaries of the advice: whether advice should be framed to benefit the society as a whole or with special concern for the most vulnerable members of the population. The third consideration involves scientific advisers' attempts to balance the strengths of the scientific evidence with the expected consequences of scientific advice. We hope to promote more explicit discussion of these issues among scientific advisers and a wider public. ( view less ) A Folkers,K Hüve,C Ammann,T Dindorf,J Kesselmeier,E Kleist,U Kuhn,R Uerlings,J Wildt Methanol emissions from several deciduous tree species with predominantly mature leaves were measured under laboratory and field conditions. The emissions were modulated by temperature and light. Under constant light conditions in the laboratory, methanol emissions increased with leaf temperature, ... ( view more )by up to 12% per degree. At constant temperatures, emissions doubled when light intensity (PAR) increased from darkness to 800 micromol x m(-2) x s(-1). A phenomenological description of light and temperature dependencies was derived from the laboratory measurements. This description was successfully applied to reproduce the diel cycle of methanol emissions from an English oak measured in the field. Labelling experiments with (13)CO(2) provided evidence that less than 10% of the emitted methanol was produced de novo by photosynthesis directly prior to emission. Hence, the light dependence of the emissions cannot be explained by instantaneous production from CO(2) fixation. Additional experiments with selective cooling of plant roots indicated that a substantial fraction of the emitted methanol may be produced in the roots or stem and transported to stomata by the transpiration stream. However, the transpiration stream cannot be considered as the main factor that determines methanol emissions by the investigated plants. ( view less ) Ramy K Aziz,Daniela Bartels,Aaron A Best,Matthew DeJongh,Terrence Disz,Robert A Edwards,Kevin Formsma,Svetlana Gerdes,Elizabeth M Glass,Michael Kubal,Folker Meyer,Gary J Olsen,Robert Olson,Andrei L Osterman,Ross A Overbeek,Leslie K McNeil,Daniel Paarmann,Tobias Paczian,Bruce Parrello,Gordon D Pusch,Claudia Reich,Rick Stevens,Olga Vassieva,Veronika Vonstein,Andreas Wilke,Olga Zagnitko BACKGROUND: The number of prokaryotic genome sequences becoming available is growing steadily and is growing faster than our ability to accurately annotate them. DESCRIPTION: We describe a fully automated service for annotating bacterial and archaeal genomes. The service identifies protein-encoding... ( view more ), rRNA and tRNA genes, assigns functions to the genes, predicts which subsystems are represented in the genome, uses this information to reconstruct the metabolic network and makes the output easily downloadable for the user. In addition, the annotated genome can be browsed in an environment that supports comparative analysis with the annotated genomes maintained in the SEED environment.The service normally makes the annotated genome available within 12-24 hours of submission, but ultimately the quality of such a service will be judged in terms of accuracy, consistency, and completeness of the produced annotations. We summarize our attempts to address these issues and discuss plans for incrementally enhancing the service. CONCLUSION: By providing accurate, rapid annotation freely to the community we have created an important community resource. The service has now been utilized by over 120 external users annotating over 350 distinct genomes. ( view less ) Rob N de Jong,Vincent Truffault,Tammo Diercks,Eiso Ab,Mark A Daniels,Rob Kaptein,Gert E FolkersThe yeast Paf1 complex consists of Paf1, Rtf1, Cdc73, Ctr9, and Leo1 and regulates histone H2B ubiquitination, histone H3 methylation, RNA polymerase II carboxy-terminal domain (CTD) Ser2 phosphorylation, and RNA 3' end processing. We provide structural insight into the Paf1 complex with the NMR st... ( view more )ructure of the conserved and functionally important Plus3 domain of human Rtf1. A predominantly beta-stranded subdomain displays structural similarity to Dicer/Argonaute PAZ domains and to Tudor domains. We further demonstrate that the highly basic Rtf1 Plus3 domain can interact in vitro with single-stranded DNA via residues on the rim of the beta sheet, reminiscent of siRNA binding by PAZ domains, but did not detect binding to double-stranded DNA or RNA. We discuss the potential role of Rtf1 Plus3 ssDNA binding during transcription elongation. ( view less ) S H Andersen,E Lykke,M B Folker,I Bernstein,S Holck Whereas the generally accepted carcinogenesis pathway of the microsatellite instabile high (MSI-H) colorectal carcinoma (CRC) involves the traditional adenoma in patients with Lynch syndrome, a serrate pathway involving serrate adenomas (SA) and sessile serrate polyps (SSP) characterize the sporadi... ( view more )c MSI-H counterpart. Recent studies have, however, challenged such simple one-pathway models, inviting the consideration of alternative, unexpected pathways. Here, the issue as to the possible role of SSP, primarily in the context of Lynch syndrome, but also in subjects from familial CRC families (FCF) is addressed. Polyps coded as hyperplastic polyps (HP) from subjects with Lynch syndrome and FCF enrolled in the HNPCC-register at the Hvidovre University Hospital as well as adenomas from this population were retrieved and reviewed for features of SSP. Ninety-eight polyps coded as HP and 41 polyps coded as adenoma from 14 individuals with Lynch syndrome as well as 17 individuals from FCF constituted the study material. Seven of the 98 polyps coded as HP displayed histological features that, to varying extent, deviated from the traditional HP (THP), yet, merely two of these, both from the FCF, were considered examples of probable SSP. None of the 41 cases coded as adenoma possessed a morphology that qualified as SSP. The prevalence of SSP was not increased as compared to the background population and thus, this serrated lesion does not appear to play a tumorigenic role in Lynch syndrome, nor in FCF. ( view less ) Thomas Burmeister,Stefan Schwartz,Almut Taubald,Edgar Jost,Thomas Lipp,Folker Schneller,Helmut Diedrich,Henrike Thomssen,Ulrich J M Mey,Jan Eucker,Harald Rieder,Nicola Gökbuget,Dieter Hoelzer,Eckhard ThielRT-PCR detects chimeric BCR-ABL mRNA in approximately 25% of adult acute lymphoblastic leukemia (ALL) cases. Minor breakpoint transcripts (e1a2) are found in about 70% of positive cases and major breakpoint transcripts (e13a2, e14a2) in about 30% of cases. However, other atypical transcripts are so... ( view more )metimes observed. We report experience gained in the GMALL Study Group and identified 8 BCR-ABL-positive adult ALL cases with such atypical transcripts: 5 with e1a3, 2 with e13a3 (b2a3), and 1 with e6a2. This corresponds to a prevalence of 1-2% of all BCR-ABL-positive cases. The clinical courses are reported and diagnostic proposals are made. ( view less ) Susanne Schneiker,Olena Perlova,Olaf Kaiser,Klaus Gerth,Aysel Alici,Matthias O Altmeyer,Daniela Bartels,Thomas Bekel,Stefan Beyer,Edna Bode,Helge B Bode,Christoph J Bolten,Jomuna V Choudhuri,Sabrina Doss,Yasser A Elnakady,Bettina Frank,Lars Gaigalat,Alexander Goesmann,Carolin Groeger,Frank Gross,Lars Jelsbak,Lotte Jelsbak,Jörn Kalinowski,Carsten Kegler,Tina Knauber,Sebastian Konietzny,Maren Kopp,Lutz Krause,Daniel Krug,Bukhard Linke,Taifo Mahmud,Rosa Martinez-Arias,Alice C McHardy,Michelle Merai,Folker Meyer,Sascha Mormann,Jose Muñoz-Dorado,Juana Perez,Silke Pradella,Shwan Rachid,Günter Raddatz,Frank Rosenau,Christian Rückert,Florenz Sasse,Maren Scharfe,Stephan C Schuster,Garret Suen,Anke Treuner-Lange,Gregory J Velicer,Frank-Jörg Vorhölter,Kira J Weissman,Roy D Welch,Silke C Wenzel,David E Whitworth,Susanne Wilhelm,Christoph Wittmann,Helmut Blöcker,Alfred Pühler,Rolf Müller The genus Sorangium synthesizes approximately half of the secondary metabolites isolated from myxobacteria, including the anti-cancer metabolite epothilone. We report the complete genome sequence of the model Sorangium strain S. cellulosum So ce56, which produces several natural products and has mo... ( view more )rphological and physiological properties typical of the genus. The circular genome, comprising 13,033,779 base pairs, is the largest bacterial genome sequenced to date. No global synteny with the genome of Myxococcus xanthus is apparent, revealing an unanticipated level of divergence between these myxobacteria. A large percentage of the genome is devoted to regulation, particularly post-translational phosphorylation, which probably supports the strain's complex, social lifestyle. This regulatory network includes the highest number of eukaryotic protein kinase-like kinases discovered in any organism. Seventeen secondary metabolite loci are encoded in the genome, as well as many enzymes with potential utility in industry. ( view less ) Norbert Zimmermann,Muhammed Kurt,Joachim Winter,Emmeran Gams,Folker Wenzel,Artur Aron Weber,Thomas Hohlfeld Platelet function and response to pharmacological inhibition are altered by cardiac surgery. For example, aggregation is increased early after aortic valve replacement (AVR) and platelet response to aspirin is often insufficient after coronary artery bypass grafting (CABG). We hypothesized that the... ( view more ) effect of aspirin administration after cardiac surgery might be impaired due to platelet activation. Therefore, the antiplatelet effect of aspirin was compared in patients (n = 20 per group) after CABG and AVR surgery (bileaflet prosthesis). Arachidonic acid-induced aggregation (turbidimetry) and thromboxane formation (radioimmunoassay) were determined before and 1, 5, and 10 days after surgery. In CABG-patients, antiplatelet treatment had been discontinued 10 days before surgery. Oral aspirin was started on day 1 after CABG. AVR-patients did not receive oral aspirin. Before surgery, platelet aggregation and thromboxane formation were significantly higher in patients with aortic stenosis. After CABG, thromboxane formation was not significantly changed from control values before surgery (66 +/- 13% on day 10) despite oral aspirin treatment, whereas thromboxane formation in patients undergoing AVR significantly increased compared to values before surgery (216 +/- 29% on day 10). In both groups of patients, 100 micromol/l aspirin in vitro largely inhibited platelet function before surgery, with markedly attenuated effects after surgery. In conclusion, thromboxane formation increased after AVR but not after CABG. The antiplatelet effect of aspirin, therefore, may be impaired after CABG by increased platelet activity. An additional in vitro "resistance" of platelets was seen after both CABG and AVR. ( view less ) Elvan Kut,Nils Schaffner,Amrei Wittwer,Victor Candia,Meike Brockmann,Claudio Storck,Gerd Folkers Pain is an experience including physiological and psychological factors. We assume that emotions may be elicited and increased through self-perceived role identity and that change of role identity alters quality and intensity of pain perception. We used role-play strategies to assess whether pain c... ( view more )an be better tolerated whenever, in an unavoidable and unpleasant context, role identity confers pain a meaningful and thus suitable character. We induced antithetic roles in 21 actors who received heat stimuli on their arms before and after role-play conditions. Pain tolerance, skin conductance and voice signals were measured. Pain tolerance increased for heroes/heroines and decreased for faint-hearts. Men showed higher pain tolerance. Heroes/heroines evaluated heat stimuli as more intense. Faint-hearts found pain stimuli more affectively loaded at lower temperatures. Women showed higher pain ratings. Hence, self-perception influences pain perception. Role-play strategies may be of value for new pain management strategies. ( view less ) Knut Brockmann,Peter Dechent,Carsten Bönnemann,Gudrun Schreiber,Jens Frahm,Folker Hanefeld Congenital muscular dystrophy (CMD) due to merosin (laminin alpha2 chain) deficiency is an autosomal recessively inherited disorder characterized by severe muscular weakness and hypotonia from birth on. Brain involvement is the rule and characterized by variable T2 hyperintensities of white matter ... ( view more )which appears swollen on cranial MRI. The pathophysiology of these white matter changes is not clear. In five patients with laminin alpha2 deficient CMD we performed short-echo time localized proton MRS with determination of absolute metabolite concentrations in grey and white matter. In affected white matter, a consistent pattern of metabolites was detected comprising reduced concentrations of N-acetylaspartate and N-acetylaspartylglutamate, creatine, and phosphocreatine, and to a milder degree of choline-containing compounds. In contrast, concentrations of myo-inositol were in the normal range. Spectra of cortical and subcortical grey matter were normal. The observed metabolite profile is consistent with white matter edema, that is reduced cellular density, and relative astrocytosis. This interpretation is in line with the hypothesis that laminin alpha2 deficiency results in leakage of fluids across the blood-brain barrier and a histopathological report of astrocytic proliferation in CMD. ( view less ) Armand Daliri,Katja Oehring,Rainer G Moosdorf,Folker E Franke,Marc Kalinowski,Faramarz Zahedi,Jens J FroelichPercutaneous computed tomographic (CT) fluoroscopy-guided biopsy was performed to evaluate an intracardiac tumor located within the left atrium of a 72-year-old woman. Postinterventional follow-up was unproblematic and free of complications. Histopathologic examination revealed a high-grade cardiac... ( view more ) sarcoma, and the patient underwent consecutive resection and radiation therapy. In general, percutaneous puncture of the heart must be considered hazardous. Under certain conditions (eg, broad-based tumor, advanced luminal mass, myocardial and/or pericardial infiltration), however, percutaneous CT-guided biopsy may be an appropriate alternative to transluminal catheter biopsy for the minimally invasive investigation of cardiac tumors. ( view less ) Folker Westphal,Thomas Junge,Peter Rösner,Giselher Fritschi,B Klein,Ulrich GirreserThis study presents and discusses the nuclear magnetic resonance (NMR) spectroscopic and mass spectroscopic data of the new designer drug 4'-methyl-alpha-pyrrolidinobutyrophenone (MPBP) and its homolog 4'-methyl-alpha-pyrrolidinohexanophenone (MPHP) which were seized in 2004 and 2000 in Germany for... ( view more ) the first time. The structure elucidation of the aliphatic part of MPBP was carried out by product ion spectroscopy of the immonium ion formed after electron ionization as well as with 1H and 13C NMR. Product ion spectroscopy of immonium ions again proved to be a powerful tool to determine the structure of designer drugs and to distinguish between isobaric structures of the alkyl-amino moiety. ( view less ) Samuel Groeschel,Knut Brockmann,Folker Hanefeld BACKGROUND: Perivascular spaces of the brain, also known as Virchow-Robin spaces (VRS), are of immunological and neuropathological relevance and can be observed in magnetic resonance images (MRI). Their histopathological significance in X-linked adrenoleukodystrophy (ALD) has been reported. Aim of ... ( view more )this study was to elucidate the prognostic or diagnostic value of VRS on MRI of the brain in the evaluation of onset or severity of the clinical course in ALD. METHODS: Clinical data and MRI from 35 patients with the cerebral form of X-ALD, 29 with the asymptomatic form (including those with adrenal insufficiency), and 36 control patients were studied retrospectively. RESULTS: VRS could be visualised by MRI in 87% of patients with asymptomatic ALD, in 80% of control patients, and in 47% of patients with cerebral ALD. None of them were found to be dilated. The number of visible VRS correlated negatively with the degree of demyelination both in patients with the cerebral and the asymptomatic form. Furthermore, in the group of patients with cerebral ALD the number of visible VRS correlated positively with a milder course of the disease. CONCLUSION: VRS on MRI of patients with ALD seem to reflect the perivascular inflammatory component of this disease. It is possible to speculate that the appearance or a higher number of visible VRS in ALD is associated with an earlier stage of the disease, or even a more benign clinical course. ( view less )
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