bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of CHOP versus CIOP in good prognosis younger patients with histologically aggressive non‐Hodgkin lymphoma
Authors: Burton C. , Smith P. , Vaughan‐Hudson G. , Qian W. , Hoskin P. , Cunningham D. , Hancock B. , Linch D.
Published: July 2005

CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) has been the standard chemotherapy regimen used for diffuse large cell lymphomas for over 30 years. Idarubicin is a 4‐demethoxy‐anthracycline analogue of daunorubicin that has proven activity in non‐Hodgkin lymphoma, and has been reported to cause less cardiotoxicity. We therefore initiated a randomised trial of standard dose CHOP versus CIOP (cyclophosphamide, idarubicin, vincristine and prednisolone), in which doxorubicin 50 mg/m2 was substituted by idarubicin 10 mg/m2, a dose thought to have equivalent anti‐lymphoma activity. This trial was closed prematurely after 211 patients had completed therapy when a lower complete remission (CR) rate was noted in the CIOP arm. The formal results with long‐term follow up are now reported. Overall response rate was 84% in the CHOP arm and 78% in the CIOP arm, CR rates were 70% and 52% respectively in all patients (P = 0·013) and 73% and 52% respectively for the eligible patients (P = 0·0084). At a median of 8 years follow‐up, 4‐year progression‐free survival for all patients was 56% in the CHOP arm and 40% in the CIOP arm (P = 0·0096). Overall survival for all patients was 65% in the CHOP arm and 56% in the CIOP arm (P = 0·14). Results for eligible patients were comparable. CIOP containing idarubicin at a dose of 10 mg/m2 is clearly inferior to standard CHOP.
Efficacy and tolerability of peginterferon alpha‐2a with or without ribavirin in thalassaemia major patients with chronic hepatitis C virus infection
Authors: Inati Adlette , Taher Ali , Ghorra Sandy , Koussa Suzanne , Taha Marwan , Aoun Elie , Sharara Ala I.
Published: July 2005

Thalassaemia patients with genotype 1 or 4 chronic hepatitis C virus (HCV) infection were randomised to receive peginterferon alpha‐2a 180 mg/week ribavirin for 48 weeks. Primary efficacy variable was sustained viral response (SVR) at 72 weeks. Thirty‐two patients were evaluated; 20 enrolled. Baseline characteristics were comparable. SVR occurred in four of 12 and five of eight patients in the monotherapy and combination groups (30% and 62·5%; P = 0·19), respectively. Undetectable RNA at 12 weeks and age <18 years were associated with improved SVR (P < 0·05). Transfusion requirements rose by 34% in the combination arm (P = 0·08). Peginterferon/ribavirin was effective in thalassaemics with HCV and moderate iron overload.
Allogeneic haematopoietic stem cell transplantation as a promising treatment for natural killer‐cell neoplasms
Authors: Murashige Naoko , Kami Masahiro , Kishi Yukiko , Kim Sung‐Won , Takeuchi Masami , Matsue Kosei , Kanda Yoshinobu , Hirokawa Makoto , Kawabata Yoshinari , Matsumura Tomoko , Kusumi Eiji , Hirabayashi Noriyuki , Nagafuji Koji , Suzuki Ritsuro , Takeuchi Kengo , Oshimi Kazuo
Published: July 2005

The efficacy of allogeneic haematopoietic stem‐cell transplantation (allo‐HSCT) for natural killer (NK)‐cell neoplasms is unknown. We investigated the results of allo‐HSCT for NK‐cell neoplasms between 1990 and 2003 through questionnaires. After reclassification by a haematopathologist, of 345 patients who underwent allo‐HSCT for malignant lymphoma, 28 had NK‐cell neoplasms (World Health Organization classification): extranodal NK/T‐cell lymphoma (n = 22), blastic NK‐cell lymphoma (n = 3), and aggressive NK‐cell leukaemia (n = 3). Twelve were chemosensitive and 16 chemorefractory. Twenty‐two had matched‐related donors. Stem‐cell source was bone marrow in eight and mobilised peripheral blood in 20. Conditioning regimens were myeloablative (n = 23) and non‐myeloablative (n = 5). Grade 2–4 acute graft‐versus‐host disease (GVHD) and chronic GVHD developed in 12 and 8 respectively. Eight died of disease progression, three of infection, two of acute GVHD, one of veno‐occlusive disease, one of interstitial pneumonitis, and one of thrombotic microangiopathy. Two‐year progression‐free and overall survivals were 34% and 40% respectively (median follow‐up, 34 months). All patients who did not relapse/progress within 10 months achieved progression‐free survival (PFS) during the follow‐up. In multivariate analysis, stem cell source (BM versus peripheral blood; relative risk 3·03), age (≥40 years vs. <40 years; relative risk 2·85), and diagnoses (extranodal NK/T‐cell lymphoma versus others; relative risk 3·94) significantly affected PFS. Allo‐HSCT is a promising treatment for NK‐cell neoplasms.
C‐reactive protein and D‐dimer with clinical probability score in the exclusion of pulmonary embolism
Authors: Steeghs N. , Goekoop R. J. , Niessen R. W. L. M. , Jonkers G. J. P. M. , Dik H. , Huisman M. V.
Published: July 2005

This study evaluated the diagnostic value of C‐reactive protein (CRP) combined with a clinical decision rule in the exclusion of pulmonary embolism (PE) and compared this with D‐dimer. In 363 consecutive outpatients CRP and D‐dimer test were performed and clinical probability of PE was assessed. Patients with D‐dimer levels <500 μg/l and clinical probability indicating ‘PE unlikely’ were followed for 3 months. Ventilation‐perfusion scan or spiral computerized tomography was performed in patients with D‐dimer levels ≥500 μg/l or clinical probability indicating ‘PE likely’. The CRP had a sensitivity of 95·7% [95% confidence interval (CI): 90–100] and negative predictive value (NPV) of 98·4% (96–100). CRP <5 mg/l with clinical probability score indicating ‘PE unlikely’ (n = 108, 30%), had a sensitivity of 96·7% (90–100), a specificity of 43·0% (37–49) and NPV of 99·1% (97–100). D‐dimer <500 μg/l with clinical probability score indicating ‘PE unlikely’ (n = 170, 51%), had a sensitivity of 96·7% (90–100), a specificity of 67·9% (62–74) and NPV of 99·4% (98–100). Based on retrospective data it was concluded that a standard CRP test can potentially be used to safely exclude PE, either as a sole test or combined with clinical probability assessment. Prospective studies are needed to confirm these findings.
The lipid A palmitoyltransferase PagP: molecular mechanisms and role in bacterial pathogenesis
Authors: Bishop Russell E.
Published: July 2005

Palmitoylated lipid A can both protect pathogenic bacteria from host immune defences and attenuate the activation of those same defences through the TLR4 signal transduction pathway. A palmitate chain from a phospholipid is incorporated into lipid A by an outer membrane enzyme PagP, which is an 8‐stranded antiparallel β‐barrel preceded by an amino‐terminal amphipathic α‐helix. The PagP barrel axis is tilted by 25° with respect to the membrane normal. An interior hydrophobic pocket in the outer leaflet‐exposed half of the molecule functions as a hydrocarbon ruler that allows the enzyme to distinguish palmitate from other acyl chains found in phospholipids. Internalization of a phospholipid palmitoyl group within the barrel appears to occur by lateral diffusion from the outer leaflet through non‐hydrogen‐bonded regions between β‐strands. The MsbA‐dependent trafficking of lipids from the inner membrane to the outer membrane outer leaflet is necessary for lipid A palmitoylation in vivo. The mechanisms by which bacteria regulate pagP gene expression strikingly reflect the corresponding pathogenic lifestyle of the bacterium. Variations on PagP structure and function can be illustrated with the known homologues from Gram‐negative bacteria, which include pathogens of humans and other mammals in addition to pathogens of insects and plants. The PagP enzyme is potentially a target for the development of anti‐infective agents, a probe of outer membrane lipid asymmetry, and a tool for the synthesis of lipid A‐based vaccine adjuvants and endotoxin antagonists.
Cell cycle arrest during S or M phase generates polarized growth via distinct signals in Candida albicans
Authors: Bachewich Catherine , Nantel Andre , Whiteway Malcolm
Published: July 2005

Treatments that perturb DNA synthesis or mitosis will activate checkpoints that prevent cell cycle progression and cell proliferation. In yeast‐form cells of the fungal pathogen Candida albicans, exposure to hydroxyurea (HU) or shutting off expression of the polo‐like kinase CaCDC5 blocked nuclear division and spindle elongation, but activated a highly polarized growth mode. We have used transcription profiling both to characterize the initiation and progression of this polar growth pattern and to determine how cell elongation may be linked to the cell cycle in C. albicans. Different gene expression patterns during early stages of cell elongation support the concept that CaCdc5p‐depleted and HU‐exposed cells were blocked at different stages of the cell cycle, and suggest that different signals may generate the common polarized growth phenotype. Consistent with this, BUB2 expression was modulated in CaCdc5p‐depleted cells, and absence of BUB2 prevented the maintenance of cell polarization, resulting in multibudded, pseudohyphal cells with constrictions. In contrast, HU‐induced filaments did not modulate or require BUB2, but were dependent on the GTPase Ras1p. However, at later stages of cell elongation, transcription profiles were more similar, and comparisons with serum‐induced hyphae revealed that the cell cycle‐arrested filaments expressed several targets of the hyphal signalling pathways. Thus, arresting the yeast cell cycle in S or M phase generates a polarized growth pattern through different mechanisms in C. albicans, and maintenance of the polar growth mode can ultimately lead to the expression of hyphal‐associated cell wall and virulence‐related factors, in the absence of any external stimuli.
Paralysis and killing of Caenorhabditis elegans by enteropathogenic Escherichia coli requires the bacterial tryptophanase gene
Authors: Anyanful Akwasi , Dolan‐Livengood Jennifer M. , Lewis Taiesha , Sheth Seema , DeZalia Mark N. , Sherman Melanie A. , Kalman Lisa V. , Benian Guy M. , Kalman Daniel
Published: July 2005

Pathogenic Escherichia coli, including enteropathogenic E. coli (EPEC), enterohaemorrhagic E. coli (EHEC), enteroinvasive E. coli (EIEC) and enterotoxigenic E. coli (ETEC) are major causes of food and water‐borne disease. We have developed a genetically tractable model of pathogenic E. coli virulence based on our observation that these bacteria paralyse and kill the nematode Caenorhabditis elegans. Paralysis and killing of C. elegans by EPEC did not require direct contact, suggesting that a secreted toxin mediates the effect. Virulence against C. elegans required tryptophan and bacterial tryptophanase, the enzyme catalysing the production of indole and other molecules from tryptophan. Thus, lack of tryptophan in growth media or deletion of tryptophanase gene failed to paralyse or kill C. elegans. While known tryptophan metabolites failed to complement an EPEC tryptophanase mutant when presented extracellularly, complementation was achieved with the enzyme itself expressed either within the pathogen or within a cocultured K12 strains. Thus, an unknown metabolite of tryptophanase, derived from EPEC or from commensal non‐pathogenic strains, appears to directly or indirectly regulate toxin production within EPEC. EPEC strains containing mutations in the locus of enterocyte effacement (LEE), a pathogenicity island required for virulence in humans, also displayed attenuated capacity to paralyse and kill nematodes. Furthermore, tryptophanase activity was required for full activation of the LEE1 promoter, and for efficient formation of actin‐filled membranous protrusions (attaching and effacing lesions) that form on the surface of mammalian epithelial cells following attachment and which depends on LEE genes. Finally, several C. elegans genes, including hif‐1 and egl‐9, rendered C. elegans less susceptible to EPEC when mutated, suggesting their involvement in mediating toxin effects. Other genes including sek‐1, mek‐1, mev‐1, pgp‐1,3 and vhl‐1, rendered C. elegans more susceptible to EPEC effects when mutated, suggesting their involvement in protecting the worms. Moreover we have found that C. elegans genes controlling lifespan (daf‐2, age‐1 and daf‐16), also mediate susceptibility to EPEC. Together, these data suggest that this C. elegans/EPEC system will be valuable in elucidating novel factors relevant to human disease that regulate virulence in the pathogen or susceptibility to infection in the host.
A tertiary structural element in S box leader RNAs is required for S‐adenosylmethionine‐directed transcription termination
Authors: McDaniel Brooke A. , Grundy Frank J. , Henkin Tina M.
Published: July 2005

The S box transcription termination control system regulates expression of genes involved in methionine metabolism. Expression of the S box regulon, comprised of 11 transcriptional units in Bacillus subtilis, is induced in response to starvation for methionine. We previously demonstrated that S‐adenosylmethionine (SAM) is the molecular effector sensed by the S box leader RNAs during transcription. A secondary structure model for S box leader RNAs was developed based on conservation of primary sequence elements and sequence covariation in helical domains. Covariation of nucleotides in two distantly spaced unpaired regions in the S box leader RNAs suggested that these two domains might interact in the RNA tertiary structure. In this study, site‐directed mutagenesis of the covarying residues in two B. subtilis S box leader sequences was employed to test the hypothesis that base‐pairing between these regions may be important. The effect of these mutations on in vivo expression, transcription termination in vitro, SAM binding, and leader RNA structure strongly supported the model that interaction between these two regions plays a key role in S box leader function. This provides the first insight into the three‐dimensional arrangement of structural elements within the S box RNAs.
Identification of a fibronectin‐binding domain within the Campylobacter jejuni CadF protein
Authors: Konkel Michael E. , Christensen Jeffrey E. , Keech Amy M. , Monteville Marshall R. , Klena John D. , Garvis Steve G.
Published: July 2005

The binding of Campylobacter jejuni to fibronectin (Fn), a component of the extracellular matrix, is mediated by a 37 kDa outer membrane protein termed CadF for Campylobacter adhesion to Fn. Previous studies have indicated that C. jejuni binds to Fn on the basolateral surface of T84 human colonic cells. To further characterize the interaction of the CadF protein with Fn, enzyme‐linked immunosorbent assays were performed to identify the Fn‐binding domain (Fn‐BD). Using overlapping 30‐mer and 16‐mer peptides derived from translated cadF nucleotide sequence, maximal Fn‐binding activity was localized to four amino acids (AA 134–137) consisting of the residues phenylalanine‐arginine‐leucine‐serine (FRLS). A mouse α‐CadF peptide polyclonal antibody (M α‐CadF peptide pAb) was generated using FRLS containing peptides and found to react with viable C. jejuni as judged by indirect fluorescent microscopy, suggesting that the FRLS residues are surface‐exposed. Binding of CadF to purified Fn and INT 407 human epithelial cells was significantly inhibited with peptides containing the Fn‐BD. Moreover, a CadF recombinant variant protein, in which the Phe‐Arg‐Leu residues (CadF AA 134–136) were altered to Ala‐Ala‐Gly, exhibited a 91% decrease in Fn‐binding activity as compared with the wild‐type CadF protein. Collectively, these data indicate that the FRLS residues (CadF AA 134–137) of the C. jejuni CadF protein possess Fn‐binding activity.
The conserved flaF gene has a critical role in coupling flagellin translation and assembly in Caulobacter crescentus
Authors: Llewellyn Midge , Dutton Rachel J. , Easter Jesse , O'Donnol Danielle , Gober James W.
Published: July 2005

The expression of the flagellin proteins in Caulobacter crescentus is regulated by the progression of flagellar assembly both at the transcriptional and post‐transcriptional levels. An early basal body structure is required for the transcription of flagellin genes, whereas the ensuing assembly of a hook structure is required for flagellin protein synthesis. Previous experiments have shown that the negative regulatory protein, FlbT, operates this second post‐transcriptional checkpoint by associating with the 5′ untranslated region (UTR) of the fljK flagellin transcript, inhibiting translation and destabilizing the mRNA. In this paper we examine the role of flaF in flagellar biogenesis. The flaF gene, which is conserved in several speices of flagellated α‐proteobacteria, is required for motility and flagellin protein synthesis. A deletion of flbT in a ΔflaF strain restored flagellin protein expression, but not motility, indicating that FlaF functions in filament assembly. Mutant strains with a deletion in flaF had no detectable fljK mRNA, the levels of which were restored by an additional mutation in flbT. Assay of fljK gene expression using transcription and translation reporter fusions indicated that FlaF was essential for the translation of fljK mRNA. FlaF protein levels were under cell cycle control, peaking during the period of flagellin expression and filament assembly, whereas FlbT was present throughout the cell cycle. These results suggest that FlbT and FlaF activities oppose one another in the regulation of flagellin expression in response to both the progression of flagellar assembly and the cell cycle.
Conservation of genes and processes controlled by the quorum response in bacteria: characterization of genes controlled by the quorum‐sensing transcription factor ComA in Bacillus subtilis
Authors: Comella Natalia , Grossman Alan D.
Published: July 2005

Quorum or diffusion responses in bacteria are mediated by secreted signalling molecules that accumulate extracellularly as cultures grow to high density. The regulatory response to these signalling molecules can result in dramatic changes in gene expression. In Bacillus subtilis, a quorum response is mediated by a secreted 10‐amino‐acid modified peptide (ComX pheromone) that activates a receptor histidine kinase (ComP) that activates a response regulator transcription factor (ComA). We have used DNA microarrays to identify genes controlled by the ComX–ComP–ComA quorum‐sensing pathway. We found that ComX, ComP and ComA affect the same set of genes, indicating that the kinase ComP is the only receptor for the signalling molecule ComX, and that ComA is the only transcription factor activated directly by ComP, under the conditions tested. Expression of over 20 genes appears to be controlled directly by this signalling pathway, and expression of over 150 additional genes, including those involved in competence development, appears to be controlled indirectly. The genes affected appear to have three general functions: (i) to co‐ordinate physiological changes involved in developmental pathways, (ii) to produce extracellular products under conditions in which high concentrations of product are needed to be effective and (iii) to enhance survival, growth and colonization under conditions of crowding or limited diffusion. Many of the genes and processes controlled by the quorum response in B. subtilis are also regulated by quorum sensing in Gram‐positive and Gram‐negative bacteria. The quorum‐sensing signalling molecules and regulatory proteins are quite different between Gram‐positives and Gram‐negatives and the convergent physiological regulation of similar genes and processes indicate the important and conserved nature of the quorum response.
Localization of RecA in Escherichia coli K‐12 using RecA–GFP
Authors: Renzette Nicholas , Gumlaw Nathan , Nordman Jared T. , Krieger Marlee , Yeh Su‐Ping , Long Edward , Centore Richard , Boonsombat Ruethairat , Sandler Steven J.
Published: July 2005

RecA is important in recombination, DNA repair and repair of replication forks. It functions through the production of a protein–DNA filament. To study the localization of RecA in live Escherichia coli cells, the RecA protein was fused to the green fluorescence protein (GFP). Strains with this gene have recombination/DNA repair activities three‐ to tenfold below wild type (or about 1000‐fold above that of a recA null mutant). RecA–GFP cells have a background of green fluorescence punctuated with up to five foci per cell. Two types of foci have been defined: 4,6‐diamidino‐2‐phenylindole (DAPI)‐sensitive foci that are bound to DNA and DAPI‐insensitive foci that are DNA‐less aggregates/storage structures. In log phase cells, foci were not localized to any particular region. After UV irradiation, the number of foci increased and they localized to the cell centre. This suggested colocalization with the DNA replication factory. recA, recB and recF strains showed phenotypes and distributions of foci consistent with the predicted effects of these mutations.
Sugar and ABA responsiveness of a minimal RBCS light‐responsive unit is mediated by direct binding of ABI4
Authors: Acevedo‐Hernández Gustavo Javier , León Patricia , Herrera‐Estrella Luis Rafael
Published: July 2005

Photosynthesis‐associated nuclear genes (PhANGs) are able to respond to multiple environmental and developmental signals, including light, sugars and abscisic acid (ABA). PhANGs have been extensively studied at the level of transcriptional regulation and several cis‐acting elements important for light responsiveness have been identified in their promoter sequences. However, the regulatory elements involved in sugar and ABA regulation of PhANGs have not been completely characterized. Using conserved modular arrangement 5 (CMA5), a previously characterized minimal light‐responsive unit, we show that in Arabidopsis thaliana this unit responds not only positively to light signals, but also negatively to sugars and ABA. The latter responses were found to be impaired in the abi4 mutant, indicating that ABSCISIC ACID INSENSITIVE‐4 (ABI4) is a regulator involved in sugar and ABA repression of this minimal regulatory unit. Furthermore, we report a new sequence element conserved in several rbcS promoters, herewith named S‐box, which is important for the sugar and ABA responsiveness of CMA5. This sequence corresponds to a putative ABI4‐binding site, which is in fact bound by the Arabidopsis ABI4 protein in vitro. The S‐box is closely associated with the G‐box present in CMA5, and this association is conserved in the promoters of several RBCS genes. This phylogenetically conserved promoter feature probably reflects a common regulatory mechanism and identifies a point of convergence between light‐ and sugar‐signaling pathways.
Ethylene regulates fast apoplastic acidification and expansin A transcription during submergence‐induced petiole elongation in Rumex palustris
Authors: Vreeburg Robert A.M. , Benschop Joris J. , Peeters Anton J.M. , Colmer Timothy D. , Ammerlaan Ankie H.M. , Staal Marten , Elzenga Theo M. , Staals Raymond H.J. , Darley Catherine P. , McQueen‐Mason Simon J. , Voesenek Laurentius A.C.J.
Published: July 2005

The semi‐aquatic dicot Rumex palustris responds to complete submergence by enhanced elongation of young petioles. This elongation of petiole cells brings leaf blades above the water surface, thus reinstating gas exchange with the atmosphere and increasing survival in flood‐prone environments. We already know that an enhanced internal level of the gaseous hormone ethylene is the primary signal for underwater escape in R. palustris. Further downstream, concentration changes in abscisic acid (ABA), gibberellin (GA) and auxin are required to gain fast cell elongation under water. A prerequisite for cell elongation in general is cell wall loosening mediated by proteins such as expansins. Expansin genes might, therefore, be important target genes in submergence‐induced and plant hormone‐mediated petiole elongation. To test this hypothesis we have studied the identity, kinetics and regulation of expansin A mRNA abundance and protein activity, as well as examined pH changes in cell walls associated with this adaptive growth. We found a novel role of ethylene in triggering two processes affecting cell wall loosening during submergence‐induced petiole elongation. First, ethylene was shown to promote fast net H+ extrusion, leading to apoplastic acidification. Secondly, ethylene upregulates one expansin A gene (RpEXPA1), as measured with real‐time RT‐PCR, out of a group of 13 R. palustris expansin A genes tested. Furthermore, a significant accumulation of expansin proteins belonging to the same size class as RpEXPA1, as well as a strong increase in expansin activity, were apparent within 4–6 h of submergence. Regulation of RpEXPA1 transcript levels depends on ethylene action and not on GA and ABA, demonstrating that ethylene evokes at least three, parallel operating pathways that, when integrated at the whole petiole level, lead to coordinated underwater elongation. The first pathway involves ethylene‐modulated changes in ABA and GA, these acting on as yet unknown downstream components, whereas the second and third routes encompass ethylene‐induced apoplastic acidification and ethylene‐induced RpEXPA1 upregulation.
EgMYB2, a new transcriptional activator from Eucalyptus xylem, regulates secondary cell wall formation and lignin biosynthesis
Authors: Goicoechea Monica , Lacombe Eric , Legay Sylvain , Mihaljevic Snjezana , Rech Philippe , Jauneau Alain , Lapierre Catherine , Pollet Brigitte , Verhaegen Daniel , Chaubet‐Gigot Nicole , Grima‐Pettenati Jacqueline
Published: July 2005

EgMYB2, a member of a new subgroup of the R2R3 MYB family of transcription factors, was cloned from a library consisting of RNA from differentiating Eucalyptus xylem. EgMYB2 maps to a unique locus on the Eucalyptus grandis linkage map and co‐localizes with a quantitative trait locus (QTL) for lignin content. Recombinant EgMYB2 protein was able to bind specifically the cis‐regulatory regions of the promoters of two lignin biosynthetic genes, cinnamoyl‐coenzyme A reductase (CCR) and cinnamyl alcohol dehydrogenase (CAD), which contain MYB consensus binding sites. EgMYB2 was also able to regulate their transcription in both transient and stable expression assays. Transgenic tobacco plants over‐expressing EgMYB2 displayed phenotypic changes relative to wild‐type plants, among which were a dramatic increase in secondary cell wall thickness, and an alteration of the lignin profiles. Transcript abundance of genes encoding enzymes specific to lignin biosynthesis was increased to varying extents according to the position of individual genes in the pathway, whereas core phenylpropanoid genes were not significantly affected. Together these results suggest a role for EgMYB2 in the co‐ordinated control of genes belonging to the monolignol‐specific pathway, and therefore in the biosynthesis of lignin and the regulation of secondary cell wall formation.
Synthesis and secondary structure of loop 4 of myelin proteolipid protein: effect of a point mutation found in Pelizaeus‐Merzbacher disease
Authors: Trifilieff E.
Published: July 2005

Abstract:  To study the effects of a point mutation found in Pelizaeus‐Merzbacher disease (PMD) on the physicochemical and structural properties of the extracellular loop 4 of the myelin proteolipid protein (PLP), we synthesized the peptide PLP(181–230)Pro215 and one mutant PLP(181–230)Ser215 with regioselective formation of the two disulphide bridges Cys200‐Cys219 and Cys183‐Cys227. As conventional amino acid building blocks failed to give crude peptides of good quality we had to optimize the synthesis by introducing pseudoproline dipeptide building blocks during the peptide elongation. In peptide Pro215 the first bridge Cys200–Cys219 was obtained after air oxidation, but in peptide Ser215 because of aggregation, dimethyl sulfoxide (DMSO) oxidation had to be used. The second bridge Cys183–Cys227 was obtained by iodine oxidation of both Cys (acetamidomethyl, Acm)‐protected peptides. The secondary structures of the parent and mutant loops were analysed by circular dichroism (CD) in the presence of trifluoroethanol (TFE) and sodium dodecyl sulphate (SDS) as a membrane mimetic. Analysis of the spectra showed that the content of α‐helix and β‐sheet varied differently for both peptides in TFE and SDS solutions, demonstrating the sensitivity of their conformation to the environment and the differences in their secondary structure. The ability of both peptides to insert into the SDS micelles was assayed by intrinsic tryptophan fluorescence.
Chemoselective synthesis of peptides containing major advanced glycation end‐products of lysine and arginine
Authors: Gruber P. , Hofmann T.
Published: July 2005

Abstract:  Useful methodologies have been developed, enabling the straightforward synthesis of peptides containing Nɛ‐(carboxymethyl)‐l‐lysine (CML) and Nɛ‐(carboxyethyl)‐l‐lysine (CEL), the major glycation end‐products of lysine. These lysine derivatives were successfully incorporated into growing peptide chains via standard Fmoc/Ot‐Bu peptide synthesis procedures. For the synthesis of peptides containing major glycation end‐products of arginine, synthetic routes have been developed enabling the transformation of ornithine residues in peptides into the well‐known arginine‐derived advanced glycation end‐products (AGEs) Glarg, carboxymethyl‐l‐arginine (CMA), MG‐H1, MG‐H2, MG‐H3, and carboxyethyl‐l‐arginine (CEA), respectively, by means of special modifying agents. Furthermore, it was shown that Glarg‐containing peptides become quantitatively hydrolyzed into CMA‐peptides under physiologic conditions. A similar reaction was observed in case of a MG‐H3‐peptide, which turned into a CEA‐peptide under these conditions.
Novel endomorphin‐2 analogs with μ‐opioid receptor antagonist activity
Authors: Kruszynski R. , Fichna J. , Do‐Rego J.‐C. , Chung N.N. , Schiller P.W. , Kosson P. , Costentin J. , Janecka A.
Published: July 2005

Abstract:  A series of position 4‐substituted endomorphin‐2 (Tyr‐Pro‐Phe‐Phe‐NH2) analogs containing 3‐(1‐naphthyl)‐alanine (1‐Nal) or 3‐(2‐naphthyl)‐alanine (2‐Nal) in l‐ or d‐configuration, was synthesized. The opioid activity profiles of these peptides were determined in the μ‐opioid receptor representative binding assay and in the Guinea‐Pig Ileum assay/Mouse Vas Deferens assay (GPI/MVD) bioassays in vitro, as well as in the mouse hot‐plate test of analgesia in vivo. In the binding assay the affinity of all new analogs for the μ‐opioid receptor was reduced compared with endomorphin‐2. The two most potent analogs were [d‐1‐Nal4]‐ and [d‐2‐Nal4]endomorphin‐2, with IC50 values 14 ± 1.25 and 19 ± 2.1 nm, respectively, compared with 1.9 ± 0.21 nm for endomorphin‐2. In the GPI assay these analogs were found to be weak antagonists and they were inactive in the MVD assay. The in vitro GPI assay results were in agreement with those obtained in the in vivo hot‐plate test. Antinociception induced by endomorphin‐2 was reversed by concomitant intracerebroventricula (i.c.v.) administration of [d‐1‐Nal4]‐ and [d‐2‐Nal4]‐endomorphin‐2, indicating that these analogs were μ‐opioid antagonists. Their antagonist activity was compared with that of naloxone. At a dose 5 μg per animal naloxone almost completely inhibited antinociceptive action of endomorphin‐2, while [d‐1‐Nal4]endomorphin‐2 in about 46%.
Influence of picloram and thidiazuron on high frequency plant regeneration in elite cultivars of wheat with long‐term retention of morphogenecity using meristematic shoot segments
Authors: Sharma V. K. , Hänsch R. , Mendel R. R. , Schulze J.
Published: July 2005

Meristematic shoot segments (MSSs) were used to develop an efficient and reproducible regeneration system via multiple shoot differentiation in two elite cultivars of winter wheal. Cylindrical basal shoot segments. 3 4 mm in length, were excised from seedlings derived from mature embryos that had been germinated directly on MS‐based medium containing growth regulators. These segments were further cultured on the same medium formulations. Out of 24 variations analysed, the combination of 2 mg1 4‐amino‐3.5,6‐trichloropicolinic acid (picloram) + 3 mg/1 thidiazuron (TDZ) was found to be the most effective in inducing clumps of multiple schools, buds with little callusing. Sectors of these clumps were (1) further multiplied by biweekly subculturing on 2 mg/l picloram + 2.5 mg/l TDZ leading lo highly differentiating green clusters of buds without loss of tnorphogenesis for more than 12 months so far. and without albinism, or (2) transferred to 0.1 nig I picloram + I mg/l TDZ for shoot development and elongation. The elongated shoots rooted on basal medium with 0.5 mg/l indole‐3‐butyric acid (IBA) were transferred to soil and showed normal growth and fertility. Both cultivars formed multiple schools ranging from 28 to 33 per responding MSS after 10 12 weeks.
A 28‐year trend of infective endocarditis associated with congenital heart diseases: A single institute experience
Authors: Takeda Sho , Nakanishi Toshio , Nakazawa Makoto
Published: July 2005

Background
: Infective endocarditis (IE) is still one of the major complications of congenital heart disease and, therefore, prevention has always been an important issue. But there has been no large scale investigation of IE in Japan.

Methods
: Clinical and microbiological features in 183 patients with congenital heart diseases complicated with infective endocarditis (IE), which were treated in our institute in the last 28 years, were reviewed.

Result
: During the period, the age distribution of the patients shifted to an older age; 80% were older than 15 years in the latest 7 year period. In the underlying diseases more complex conditions increased, such as the post Rastelli operation. Dental or oral diseases were the major preceding events and Streptococcus was the major pathogen throughout the study periods in the data.

Conclusion
: The result indicates the importance of continuing education for the prevention of IE and oral hygiene especially in adult patients with a risk for IE.
Epidemiologic picture of Kawasaki disease in Korea, 2000–2002
Authors: Park Yong Won , Han Ji whan , Park In Sook , Kim Chang Hwi , Yun Yong Soo , Cha Sung Ho , Ma Jae Sook , Lee Sang Bum , Kim Chul Ho , Lee Heung Jae , Tockgo Young Chang
Published: July 2005

Background
: The aim of this study was to investigate the incidence rate and epidemiologic patterns of Kawasaki disease in Korea for a 3 year period during 2000 to 2002.

Methods
: An epidemiologic survey on Kawasaki disease was retrospectively performed. The questionnaire was sent to all 112 hospitals having pediatric residency programs, and obtained data were analyzed.

Results
: The 9150 cases of Kawasaki disease from 92 hospitals which responded (response rate, 82.1%) included 5515 males and 3635 females (male : female ratio, 1.52:1). The incidence rate per 100 000 children <5 years old was 73.7 in 2000, and increased to 90.8 in 2001, and 95.5 in 2002 (average rate, 86.4). The monthly number of patients was slightly higher in May, June and July. Their mean age of onset, the proportion of sibling cases, and a rate of recurrent cases were 30.5 months, 0.17%, and 2.9%, respectively. Coronary arterial abnormalities occurred in 18.6% of cases including dilatations of 17.3% and aneurysms of 3.1%.

Conclusion
: The average annual incidence, 86.4/100 000 in children <5 years old is the second highest rate in the world.
Risk factors for the different types of chronic lung diseases of prematurity according to the preceding respiratory distress syndrome
Authors: Choi Chang Won , Kim Beyong Il , Park June Dong , Koh Young Yull , Choi Jung‐Hwan , Choi Jung Yun
Published: July 2005

Background
: Recently, atypical chronic lung disease (CLD) of prematurity that develops in the absence of preceding respiratory distress syndrome (RDS) have been observed frequently. The specific risk factors for atypical CLD that are presumed to be different from those for classical CLD that develops following RDS were assessed.

Methods
: Prospective cohort analysis was done from 115 very low‐birthweight infants who were born in Seoul National University Hospital, Seoul, Korea, and survived more than 36 weeks postmenstrual age or 28 days of life. All subjects were classified into either a preceding RDS group (n = 35) or a non‐RDS group (n = 80). Logistic regression analysis was done for the multivariate assessment of specific risk factors for CLD in both groups.

Results
: The analysis showed that short gestational age (GA; relative risk [RR], 3.1 per 1 week decrement; 95% confidence intervals [CI], 2.7–3.4), of the male gender (RR, 9.8; CI, 0.9–112), and poor response to surfactant (RR, 14; CI, 1.2–156) were significant risk factors for CLD in the preceding RDS group. In the non‐RDS group, chorioamnionitis was one of the significant risk factors for CLD (RR, 4.8; CI, 1.1–21) along with short GA and high mean airway pressure (MAP) during the first 3 days of life.

Conclusion
: Chorioamnionitis was a risk factor for atypical CLD in addition to short GA and high MAP during the early postnatal period, and poor response to surfactant was a risk factor for classical CLD in addition to short GA and being male. Therefore, CLD is considered to have type‐specific risk factors.
The relationship between autonomic nervous activity and physical activity in children
Authors: Iwasa Yukie , Nakayasu Kimiko , Nomura Masahiro , Nakaya Yutaka , Saito Ken , Ito Susumu
Published: July 2005

Background
: There have been few studies that have reported on heart rate variability and the development of autonomic nervous function in children. This study investigated the relationship between heart rate variabilities at night and physical activity in children.

Methods
: The study subjects were 29 children, including 17 boys and 12 girls. The daily activity product and heart rate variabilities during sleep at night (00.00–05.00 hours) were measured and several aspects of these parameters were analyzed. In one child (an 8‐year‐old girl), heart rate variability and the physical activity product were measured for 12 days.

Results
: There was a negative correlation between the mean R–R interval and the duration (min) of heavy exercise per day (r = −0.39, P < 0.05). In the 8‐year‐old girl, from whom data was obtained for 12 days, the duration of heavy exercise per day was negatively correlated with the mean R–R interval (r = −0.63, P < 0.05), the number of changes in successive R–R intervals greater than 50 msec (RR50) (r = −0.74, P < 0.01), and the high frequency (HF) component (r = −0.66, P < 0.05). Furthermore, the daily number of steps was negatively correlated with the mean R–R interval (r = −0.66, P < 0.05), RR50 (r = −0.71, P < 0.05) and the HF component (r = −0.66, P < 0.05). There was a negative correlation between the amounts of energy consumption and the mean R–R interval (r = −0.69, P < 0.05). There was a negative correlation between the amounts of energy consumption and RR50 (r = −0.76, P < 0.01). Moreover, there was also a negative correlation between the amount of energy consumption and the HF component (r = −0.71, P < 0.05).

Conclusion
: These findings suggested that physical activities increase heart rate during sleep, but reduce parasympathetic nervous activity at night. Because both the HF component and RR50 reduce with growth, the exercise‐related inhibition of parasympathetic nervous activity may be a developmental stimulus to reach a balanced autonomic nervous pattern in adults.
Treatment of intestinal perforation in extremely low‐birthweight infants
Authors: Kawakami Akihiro , Shirakawa Yoshitsugu , Shirahata Akira , Yano Kouichi , Morita Masaru , Yasumoto Kimimasa
Published: July 2005

Background
: The mortality of intestinal perforation in extremely low‐birthweight infants (ELBWI) is high. It still remains to be determined whether peritoneal drainage is a definitive treatment instead of laparotomy. The authors used bedside peritoneal drainage (BSPD) as the diagnostic procedure, and exchange transfusion (ET) as the preparatory procedure for invasive stress of laparotomy. The treatment protocol is composed primarily of laparotomy combined with BSPD and ET.

Methods
: ELBWI who developed intestinal perforation during hospitalization between 1993 and 2000 were treated according to the aforementioned protocol. Their medical records were examined retrospectively.

Results
: Eight ELBWI were identified. The subjects' birthweights ranged from 553 to 892 g and the gestational age ranged from 23 to 26 weeks. The subjects consisted of five cases with idiopathic intestinal perforation, two cases with necrotizing enterocolitis, and one case with meconium plug syndrome. Laparotomy was performed in all cases, and BSPD was performed in seven cases. Intestinal perforation was definitively diagnosed by X‐ray only in three cases, while by stool‐like drainage in BSPD in the other five cases. Seven (87.5%) cases survived.

Conclusion
: In this limited experience, the treatment mainly composed of laparotomy combined with BSPD and ET appeared beneficial.
Which is the ‘Self’ in ‘Self-Interest’?
Authors: duGay Paul
Published: July 2005

This article contends that homogenisation of the term ‘self-interest’ – in sociological and economic discourse – has resulted in many misconceptions about what particular doctrines of ‘self-interest’ were instituted to achieve at certain historical periods and in specific cultural milieux. At its worst, the article argues, this has led to a misunderstanding of the import of particular doctrines of self interest, which are read in terms of general tradition – such as that which views self-interested conduct as a natural faculty – rather than in terms of the context specific aims of those advocating them. The article attempts to show how, historically, there have been quite significant changes in the characterisation of the ‘self’ deemed to be ‘self-interested’. In particular, it focuses on the ‘self’ of certain early modern conceptions of self interest, and suggests this creation is best viewed not as a subjectivity transcendentally presupposed by experience, but as one historically cultivated to counter the exigencies of particular circumstances – the disaster of perpetual ‘warre’ in 17th century Europe – and to meet the purposes of a certain way of life – existence in the civitas.
Disgusted Subjects: The Making of Middle-Class Identities
Authors: Lawler Stephanie
Published: July 2005

Although the classed dimensions of ‘taste’ have, following Bourdieu, been widely discussed, expressions of disgust at perceived violations of taste have been less frequently considered in relation to class. This paper considers various expressions of disgust at white working-class existence and explores what they might tell us about middle-class identities and identifications. I argue that the narratives of decline and of lack present in such representations can be seen in terms of a long-standing middle-class project of distinguishing itself. Drawing on Bourdieu's critique of Kantian aesthetics, I argue that the ownership of ‘taste’ is understood as reflecting true humanity, and as conferring uniqueness. Ironically, however, this uniqueness is only achieved through an incorporation of collective, classed understandings. The paper calls for a problematization of a normative and normalized middle-class location that is, I argue, given added legitimacy by a perceived decline in the significance of class itself.

[A]n account of class, rank or social hierarchy must be thin indeed unless accompanied by an account of the passions and sentiments that sustain it (William Miller, The Anatomy of Disgust, p. 245).

Social identity lies in difference, and difference is asserted against what is closest, which represents the greatest threat (Pierre Bourdieu, Distinction, p. 479).

What we read as objective class divisions are produced and maintained by the middle class in the minutiae of everyday practice, as judgements of culture are put into effect (Beverley Skeggs, Class, Self, Culture, p. 118).
Coming Out at Work: Performativity and the Recognition and Renegotiation of Identity
Authors: Ward James , Winstanley Diana
Published: July 2005

This paper is about ‘coming out’ and the process of disclosure and non-disclosure of minority sexual identity in organizations. The process of ‘coming out’ is important for the individual lesbian or gay man since it is concerned with the discursive recognition and renegotiation of their identity. The study uses storytelling and a double narrative approach, where 92 individuals were interviewed to produce 15 stories of coming out, which were used for discussion in focus groups. The research took place within 6 organizations – 2 emergency services, the police and the fire service, 2 civil service departments and 2 banks. A conceptual framework is developed to explain the process of disclosure, showing it to be a continuing process rather than a single event. The concept of performativity is used to explain how in coming out the discursive practice and the telling of sexuality performs the act of coming out, making it an illocutionary speech act, and one which is made as an active or forced choice. The performative and perlocutionary speech acts interact with available subject positions thereby impacting on the individual's subjectivity. Sexuality is an under-researched area of diversity in work organizations, as well as being one of the most difficult to research, so the level of access afforded by this research and the framework it produces provides a significant contribution to our understanding of minority sexual identity at work.
Evidence for increased expression of the vesicular glutamate transporter, VGLUT1, by a course of antidepressant treatment
Authors: Tordera Rosa M. , Pei Qi , Sharp Trevor
Published: July 2005

The therapeutic effect of a course of antidepressant treatment is believed to involve a cascade of neuroadaptive changes in gene expression leading to increased neural plasticity. Because glutamate is linked to mechanisms of neural plasticity, this transmitter may play a role in these changes. This study investigated the effect of antidepressant treatment on expression of the vesicular glutamate transporters, VGLUT1–3 in brain regions of the rat. Repeated treatment with fluoxetine, paroxetine or desipramine increased VGLUT1 mRNA abundance in frontal, orbital, cingulate and parietal cortices, and regions of the hippocampus. Immunoautoradiography analysis showed that repeated antidepressant drug treatment increased VGLUT1 protein expression. Repeated electroconvulsive shock (ECS) also increased VGLUT1 mRNA abundance in regions of the cortex and hippocampus compared to sham controls. The antidepressant drugs and ECS did not alter VGLUT1 mRNA abundance after acute administration, and no change was detected after repeated treatment with the antipsychotic agents, haloperidol and chlorpromazine. In contrast to VGLUT1, the different antidepressant treatments did not commonly increase the expression of VGLUT2 or VGLUT3 mRNA. These data suggest that a course of antidepressant drug or ECS treatment increases expression of VGLUT1, a key gene involved in the regulation of glutamate secretion.
Multiple calcium channels and kinases mediate α7 nicotinic receptor neuroprotection in PC12 cells
Authors: Ren Ke , Puig Viviana , Papke Roger L. , Itoh Yoshitsugu , Hughes Jeffrey A. , Meyer Edwin M.
Published: July 2005

α7 Nicotinic receptors are calcium permeant and provide neuroprotection against many insults. We investigated the roles of intracellular calcium ions and downstream calcium channels in this protection. The α7 agonist GTS‐21 prevented pheochromocytoma cell death induced by nerve growth factor + serum deprivation over a 3‐day interval. This effect was blocked by the intracellular calcium chelator 1,2‐bis(2‐aminophenoxy)ethane‐N,N,N′,N′‐tetraacetic acid in a manner that did not appear to involve changes in receptor density. 1,2‐Bis(2‐aminophenoxy)ethane‐N,N,N′,N′‐tetraacetic acid blocked GTS‐21‐induced protein kinase C activation, a necessary process for protection. The insositol triphosphate calcium‐channel blocker xestospongin C and the phospholipases C inhibitor U‐73122 blocked protection, ryanodine partially attenuated protection, but the L‐type channel antagonist nifedipine had no effect. ERK1/2 but not JNK and p38 were activated by GTS‐21, and the ERK phosphorylation inhibitors PD98059 and U0126 blocked protection.