bluuebunny/crossref_metadata_2025 huggingface dataset:
The Neuropsychology of Cannabis and other Substance use in Schizophrenia: Review of the Literature and Critical Evaluation of Methodological Issues
Authors: Coulston Carissa M. , Perdices Michael , Tennant Christopher C.
Published: October 2007

Research on the neuropsychology of substance use in schizophrenia has been steadily growing over the past decade. However, significant gaps remain in the knowledge of individual substances and their relationship to cognition in the schizophrenia spectrum disorders. Approximately 65 studies to date have directly examined this relationship. Of these, approximately 20 have focused on nicotine, 15 on alcohol, 10 on cocaine, three on stimulants/hallucinogens, one on benzodiazepines, 10 on polydrug abuse, and seven on cannabis. Research on cannabis is especially lacking, given that worldwide it is the most commonly used illicit drug in schizophrenia, is used at higher rates in schizophrenia than in the general population, and makes its own unique contribution to the onset and prognosis of schizophrenia. In the present paper an overview of the neuropsychology literature on substance use in schizophrenia is presented, with special emphasis on cannabis. This incorporates a discussion of the methodological limitations inherent in these studies, and range of potential confounding variables that were not considered or controlled, providing directions for future research into the cognitive correlates of cannabis and other substance use in schizophrenia.
Increased Anterior Cingulate Cortex Volume in Bipolar I Disorder
Authors: Javadapour Ali , Malhi Gin S. , Ivanovski Belinda , Chen Xiaohua , Wen Wei , Sachdev Perminder
Published: October 2007

Objective: Functional neuroimaging studies have implicated the anterior cingulate cortex (ACC) in the pathophysiology of bipolar disorder (BD), but findings from volumetric studies have been less consistent, therefore the purpose of the present study was to further investigate the existence of volumetric abnormalities in the ACC cortex of individuals with BD. In addition to methodological inconsistencies many previous studies have been lacking robustness clinically with respect to characterizing bipolar patients and comparison subjects. Hence, the present study matched the groups closely across a number of demographic parameters.

Methods: Using magnetic resonance imaging, ACC volumes of 24 bipolar patients were compared to 24 gender-, age-, and education-matched control subjects, and these findings were further investigated in relation to both illness and treatment factors.

Results: A significantly larger (26%) right ACC in bipolar patients than control subjects was seen, and this difference was not associated with a history of psychosis, familiality, or lithium treatment, after controlling for potential confounds. Patients reporting fewer affective episodes did, however, have significantly larger ACC volumes than controls, suggesting ACC volumetric changes early in the course of BD.

Conclusions: An increase in the size of the ACC may have important implications for the neurobiology of BD. It is suggested that attempts to control affective instability during the early stages of the illness necessitates greater ACC mediation via its role in conflict resolution and hence this is reflected in the increased size of the ACC early in the course of the illness.
Impact of Co-Occurring Substance use on 6 Month Outcomes for Young People Seeking Mental Health Treatment
Authors: Baker Kathryn D. , Lubman Dan I. , Cosgrave Elizabeth M. , Killackey Eoin J. , Pan Yuen Hok , Hides Leanne , Baksheev Gennady N. , Buckby Joe A. , Yung Alison R.
Published: October 2007

Objective: Co-occurring substance use and mental health disorders are highly prevalent among young people attending services, yet few studies have examined the effect of such comorbidity among those referred for treatment. The aim of the current study was to examine the impact of co-occurring substance use disorders (SUDs) on 6 month outcomes for young people seeking mental health treatment.

Method: One hundred and six young people (aged 15–24 years) with a non-psychotic DSM-IV Axis I disorder were assessed following referral to a specialist youth public mental health service. Participants were given a structured interview, as well as questionnaires assessing drug use, psychopathology, psychosocial functioning and self-esteem at baseline and 6 month follow up.

Results: At baseline, 23 participants met criteria for a co-occurring SUD and 83 had a non-psychotic Axis I disorder. Both the non-SUD and the co-occurring SUD groups had high levels of psychopathology, serious impairments in functioning and moderate levels of suicidal ideation, although those with co-occurring SUD had significantly poorer levels of functioning. At 6 month follow up the co-occurring SUD group continued to experience substantial problems with symptoms and functioning whereas the non-SUD group had significant improvement in both of these domains.

Conclusions: The present findings are consistent with studies examining the impact of co-occurring substance use and mental health issues across different treatment settings, and reinforce recommendations that young people with co-occurring disorders require more intensive and integrated interventions. The present findings also highlight the need for routine assessment and management of substance use issues within youth mental health settings.
Delusions Incorporating Cannabis use in Dually Diagnosed Patients with a Primary Psychotic Disorder
Authors: Flanders Sarah E.
Published: October 2007

Objective: To describe and discuss the implications for treatment of 3 cases of dually diagnosed patients with a primary psychotic disorder who have developed persisting, cannabis-oriented delusional systems.

Method: Psychiatric assessment and daily observation on an acute inpatient psychiatric unit.

Results: Abstinence appears to be particularly difficult to attain for a patient with psychosis who hold delusional beliefs that cannabis is a conduit for supernormal experiences with positive affective content, grandiose themes and a sense of enhanced self-efficacy.

Conclusion: This phenomenon poses special challenges in the treatment of dual diagnosis patients. Modifications to existing CBT protocols for the treatment of substance abuse in psychosis might be useful in such patients.
Functional interactions between BLM and XRCC3 in the cell
Authors: Otsuki Makoto , Seki Masayuki , Inoue Eri , Yoshimura Akari , Kato Genta , Yamanouchi Saki , Kawabe Yoh-ichi , Tada Shusuke , Shinohara Akira , Komura Jun-ichiro , Ono Tetsuya , Takeda Shunichi , Ishii Yutaka , Enomoto Takemi
Published: October 2007

Bloom's syndrome (BS), which is caused by mutations in the BLM gene, is characterized by a predisposition to a wide variety of cancers. BS cells exhibit elevated frequencies of sister chromatid exchanges (SCEs), interchanges between homologous chromosomes (mitotic chiasmata), and sensitivity to several DNA-damaging agents. To address the mechanism that confers these phenotypes in BS cells, we characterize a series of double and triple mutants with mutations in BLM and in other genes involved in repair pathways. We found that XRCC3 activity generates substrates that cause the elevated SCE in blm cells and that BLM with DNA topoisomerase IIIα suppresses the formation of SCE. In addition, XRCC3 activity also generates the ultraviolet (UV)- and methyl methanesulfonate (MMS)–induced mitotic chiasmata. Moreover, disruption of XRCC3 suppresses MMS and UV sensitivity and the MMS- and UV-induced chromosomal aberrations of blm cells, indicating that BLM acts downstream of XRCC3.
Cells migrating to sites of tissue damage in response to the danger signal HMGB1 require NF-κB activation
Authors: Palumbo Roberta , Galvez Beatriz G. , Pusterla Tobias , De Marchis Francesco , Cossu Giulio , Marcu Kenneth B. , Bianchi Marco E.
Published: October 2007

Tissue damage is usually followed by healing, as both differentiated and stem cells migrate to replace dead or damaged cells. Mesoangioblasts (vessel-associated stem cells that can repair muscles) and fibroblasts migrate toward soluble factors released by damaged tissue. Two such factors are high mobility group box 1 (HMGB1), a nuclear protein that is released by cells undergoing unscheduled death (necrosis) but not by apoptotic cells, and stromal derived factor (SDF)–1/CXCL12. We find that HMGB1 activates the canonical nuclear factor κB (NF-κB) pathway via extracellular signal-regulated kinase phosphorylation. NF-κB signaling is necessary for chemotaxis toward HMGB1 and SDF-1/CXCL12, but not toward growth factor platelet-derived growth factor, formyl-met-leu-phe (a peptide that mimics bacterial invasion), or the archetypal NF-κB–activating signal tumor necrosis factor α. In dystrophic mice, mesoangioblasts injected into the general circulation ingress inefficiently into muscles if their NF-κB signaling pathway is disabled. These findings suggest that NF-κB signaling controls tissue regeneration in addition to early events in inflammation.
Two regulatory steps of ER-stress sensor Ire1 involving its cluster formation and interaction with unfolded proteins
Authors: Kimata Yukio , Ishiwata-Kimata Yuki , Ito Tatsuhiko , Hirata Aiko , Suzuki Tomohide , Oikawa Daisuke , Takeuchi Masato , Kohno Kenji
Published: October 2007

Chaperone protein BiP binds to Ire1 and dissociates in response to endoplasmic reticulum (ER) stress. However, it remains unclear how the signal transducer Ire1 senses ER stress and is subsequently activated. The crystal structure of the core stress-sensing region (CSSR) of yeast Ire1 luminal domain led to the controversial suggestion that the molecule can bind to unfolded proteins. We demonstrate that, upon ER stress, Ire1 clusters and actually interacts with unfolded proteins. Ire1 mutations that affect these phenomena reveal that Ire1 is activated via two steps, both of which are ER stress regulated, albeit in different ways. In the first step, BiP dissociation from Ire1 leads to its cluster formation. In the second step, direct interaction of unfolded proteins with the CSSR orients the cytosolic effector domains of clustered Ire1 molecules.
Regulatory interactions between two actin nucleators, Spire and Cappuccino
Authors: Quinlan Margot E. , Hilgert Susanne , Bedrossian Anaid , Mullins R. Dyche , Kerkhoff Eugen
Published: October 2007

Spire and Cappuccino are actin nucleation factors that are required to establish the polarity of Drosophila melanogaster oocytes. Their mutant phenotypes are nearly identical, and the proteins interact biochemically. We find that the interaction between Spire and Cappuccino family proteins is conserved across metazoan phyla and is mediated by binding of the formin homology 2 (FH2) domain from Cappuccino (or its mammalian homologue formin-2) to the kinase noncatalytic C-lobe domain (KIND) from Spire. In vitro, the KIND domain is a monomeric folded domain. Two KIND monomers bind each FH2 dimer with nanomolar affinity and strongly inhibit actin nucleation by the FH2 domain. In contrast, formation of the Spire–Cappuccino complex enhances actin nucleation by Spire. In Drosophila oocytes, Spire localizes to the cortex early in oogenesis and disappears around stage 10b, coincident with the onset of cytoplasmic streaming.
A lipid transfer protein that transfers lipid
Authors: Levine Tim P.
Published: October 2007

Very few lipid transfer proteins (LTPs) have been caught in the act of transferring lipids in vivo from a donor membrane to an acceptor membrane. Now, two studies (Halter, D., S. Neumann, S.M. van Dijk, J. Wolthoorn, A.M. de Maziere, O.V. Vieira, P. Mattjus, J. Klumperman, G. van Meer, and H. Sprong. 2007. J. Cell Biol. 179:101–115; D'Angelo, G., E. Polishchuk, G.D. Tullio, M. Santoro, A.D. Campli, A. Godi, G. West, J. Bielawski, C.C. Chuang, A.C. van der Spoel, et al. 2007. Nature. 449:62–67) agree that four-phosphate adaptor protein 2 (FAPP2) transfers glucosylceramide (GlcCer), a lipid that takes an unexpectedly circuitous route.
Improved BLAST searches using longer words for protein seeding
Authors: Shiryev Sergey A. , Papadopoulos Jason S. , Schäffer Alejandro A. , Agarwala Richa
Published: October 2007

Motivation: The blastp and tblastn modules of BLAST are widely used methods for searching protein queries against protein and nucleotide databases, respectively. One heuristic used in BLAST is to consider only database sequences that contain a high-scoring match of length at most 5 to the query. We implemented the capability to use words of length 6 or 7. We demonstrate an improved trade-off between running time and retrieval accuracy, controlled by the score threshold used for short word matches. For example, the running time can be reduced by 20-30% while achieving ROC (receiver operator characteristic) scores similar to those obtained with current default parameters.

Availability: The option to use long words is in the NCBI C and C++ toolkit code for BLAST, starting with version 2.2.16 of blastall. A Linux executable used to produce the results herein is available at: ftp://ftp.ncbi.nlm.nih.gov/pub/agarwala/protein_longwords

Contact:  richa@helix.nih.gov
Four-Body Scoring Function for Mutagenesis
Authors: Deutsch Chris , Krishnamoorthy Bala
Published: October 2007

Motivation: There is a need for an efficient and accurate computational method to identify the effects of single- and multiple-residue mutations on the stability and reactivity of proteins. Such a method should ideally be consistent and yet applicable in a widespread manner, i.e. it should be applied to various proteins under the same parameter settings, and have good predictive power for all of them.

Results: We develop a Delaunay tessellation-based four-body scoring function to predict the effects of single- and multiple-residue mutations on the stability and reactivity of proteins. We test our scoring function on sets of single-point mutations used by several previous studies. We also assemble a new, diverse set of 237 single- and multiple-residue mutations, from over 24 different publications. The four-body scoring function correctly predicted the changes to the stability of 169 out of 210 mutants (80.5%), and the changes to the reactivity of 17 out of 27 mutants (63%). For the mutants that had the changes in stability/reactivity quantified (using reaction rates, temperatures, etc.), an average Spearman rank correlation coefficient of 0.67 was achieved with the four-body scores. We also develop an efficient method for screening huge numbers of mutants of a protein, called combinatorial mutagenesis. In one study, 64 million mutants of a cold-shock nucleus binding domain protein 1CSQ, with six of its residues being changed to all possible (20) amino acids, were screened within a few hours on a PC, and all five stabilizing mutants reported were correctly identified as stabilizing by combinatorial mutagenesis.

Availability: All lists of mutants scored, and executables of programs developed as part of this study are available from this web page: http://www.wsu.edu/~kbala/Mutate.html

Contact:  kbala@wsu.edu or bkrishna@math.wsu.edu

Supplementary information: Supplementary data are available at Bioinformatics online.
Extracting three-way gene interactions from microarray data
Authors: Zhang Jiexin , Ji Yuan , Zhang Li
Published: October 2007

Motivation: It is an important and difficult task to extract gene network information from high-throughput genomic data. A common approach is to cluster genes using pairwise correlation as a distance metric. However, pairwise correlation is clearly too simplistic to describe the complex relationships among real genes since co-expression relationships are often restricted to a specific set of biological conditions/processes. In this study, we described a three-way gene interaction model that captures the dynamic nature of co-expression relationship between a gene pair through the introduction of a controller gene.

Results: We surveyed 0.4 billion possible three-way interactions among 1000 genes in a microarray dataset containing 678 human cancer samples. To test the reproducibility and statistical significance of our results, we randomly split the samples into a training set and a testing set. We found that the gene triplets with the strongest interactions (i.e. with the smallest P-values from appropriate statistical tests) in the training set also had the strongest interactions in the testing set. A distinctive pattern of three-way interaction emerged from these gene triplets: depending on the third gene being expressed or not, the remaining two genes can be either co-expressed or mutually exclusive (i.e. expression of either one of them would repress the other). Such three-way interactions can exist without apparent pairwise correlations. The identified three-way interactions may constitute candidates for further experimentation using techniques such as RNA interference, so that novel gene network or pathways could be identified.

Contact:  lzhangli@mdanderson.org

Supplementary information:  http://odin.mdacc.tmc.edu/~zhangli/ThreeWay
Evaluation and integration of 49 genome-wide experiments and the prediction of previously unknown obesity-related genes
Authors: English Sangeeta B. , Butte Atul J.
Published: October 2007

Motivation: Genome-wide experiments only rarely show resounding success in yielding genes associated with complex polygenic disorders. We evaluate 49 obesity-related genome-wide experiments with publicly available findings including microarray, genetics, proteomics and gene knock-down from human, mouse, rat and worm, in terms of their ability to rediscover a comprehensive set of genes previously found to be causally associated or having variants associated with obesity.

Results: Individual experiments show poor predictive ability for rediscovering known obesity-associated genes. We show that intersecting the results of experiments significantly improves the sensitivity, specificity and precision of the prediction of obesity-associated genes. We create an integrative model that statistically significantly outperforms all 49 individual genome-wide experiments. We find that genes known to be associated with obesity are significantly implicated in more obesity-related experiments and use this to provide a list of genes that we predict to have the highest likelihood of association for obesity. The approach described here can include any number and type of genome-wide experiments and might be useful for other complex polygenic disorders as well.

Contact:  abutte@stanford.edu

Supplementary information: Available online and at http://buttelab.stanford.edu/doku.php?id=public:obesityintegration
Biclustering as a method for RNA local multiple sequence alignment
Authors: Wang Shu , Gutell Robin R. , Miranker Daniel P.
Published: October 2007

Motivations: Biclustering is a clustering method that simultaneously clusters both the domain and range of a relation. A challenge in multiple sequence alignment (MSA) is that the alignment of sequences is often intended to reveal groups of conserved functional subsequences. Simultaneously, the grouping of the sequences can impact the alignment; precisely the kind of dual situation biclustering is intended to address.

Results: We define a representation of the MSA problem enabling the application of biclustering algorithms. We develop a computer program for local MSA, BlockMSA, that combines biclustering with divide-and-conquer. BlockMSA simultaneously finds groups of similar sequences and locally aligns subsequences within them. Further alignment is accomplished by dividing both the set of sequences and their contents. The net result is both a multiple sequence alignment and a hierarchical clustering of the sequences.

BlockMSA was tested on the subsets of the BRAliBase 2.1 benchmark suite that display high variability and on an extension to that suite to larger problem sizes. Also, alignments were evaluated of two large datasets of current biological interest, T box sequences and Group IC1 Introns. The results were compared with alignments computed by ClustalW, MAFFT, MUCLE and PROBCONS alignment programs using Sum of Pairs (SPS) and Consensus Count.

Results for the benchmark suite are sensitive to problem size. On problems of 15 or greater sequences, BlockMSA is consistently the best. On none of the problems in the test suite are there appreciable differences in scores among BlockMSA, MAFFT and PROBCONS. On the T box sequences, BlockMSA does the most faithful job of reproducing known annotations. MAFFT and PROBCONS do not. On the Intron sequences, BlockMSA, MAFFT and MUSCLE are comparable at identifying conserved regions.

Availability: BlockMSA is implemented in Java. Source code and supplementary datasets are available at http://aug.csres.utexas.edu/msa/

Contact:  shuwang2006@gmail.com

Supplementary information: Supplementary data are available at Bioinformatics online.
BiasViz: visualization of amino acid biased regions in protein alignments
Authors: Huska Matthew R. , Buschmann Henrik , Andrade-Navarro Miguel A.
Published: October 2007

Summary: About a third of all protein sequences have at least one composition biased region (CBR). Such regions might act as linkers between protein domains but often confer specific binding to various molecules; therefore, their characterization in terms of their boundaries and over-represented residues is important. Analysis of CBRs in a particular sequence can be time consuming if several types of biases have to be explored and their position visualized. Assessment of the significance of the detected CBRs can be approached by comparison to homologous protein sequences. To assist this procedure, we have developed BiasViz, a tool that allows to graphically studying local amino acid composition in protein sequences of a multiple sequence alignment.

Availability: BiasViz java applet and source code can be accessed from http://biasviz.sourceforge.net

Contact:  matthuska@alumni.uwaterloo.ca
HMM-Kalign: a tool for generating sub-optimal HMM alignments
Authors: Becker Emmanuelle , Cotillard Aurélie , Meyer Vincent , Madaoui Hocine , Guérois Raphaël
Published: October 2007

Summary: Recent development of strategies using multiple sequence alignments (MSA) or profiles to detect remote homologies between proteins has led to a significant increase in the number of proteins whose structures can be generated by comparative modeling methods. However, prediction of the optimal alignment between these highly divergent homologous proteins remains a difficult issue. We present a tool based on a generalized Viterbi algorithm that generates optimal and sub-optimal alignments between a sequence and a Hidden Markov Model. The tool is implemented as a new function within the HMMER package called hmmkalign.

Availability:  http://www-spider.cea.fr/Groups/hk3039/view.html

Supplementary information: Supplementary data are available at Bioinformatics online.
Organizational Culture and Organizational Change: The Transformation of Savings Banks in Denmark, 1965–1990
Authors: Hansen Per H.
Published: October 2007

In this article, I argue that organizations' historical narratives are a basic and important component of their culture and identity, and that these narratives can be resources as well as constraints. I combine a narrative approach with Joanne Martin's three perspective theory of organizational culture, and using the transformation of Danish savings banks as a case, I demonstrate how a narrative approach can provide a new and better understanding of organizational behaviour and change than mainstream economics and the abundant functionalist organizational culture literature. I demonstrate how, when change was called for by external pressures, the savings banks choice set was constrained by a shared narrative about their historical origins. This narrative, in turn, constituted the identity, image and organizational culture of savings banks and to a high degree restrained learning capabilities, created organizational inertia and delayed the adoption of a new strategy.
Stability of Barley stripe mosaic virus–Induced Gene Silencing in Barley
Authors: Bruun-Rasmussen Marianne , Madsen Christian Toft , Jessing Stine , Albrechtsen Merete
Published: October 2007

Virus-induced gene silencing (VIGS) can be used as a powerful tool for functional genomics studies in plants. With this approach, it is possible to target most genes and downregulate the messenger (m)RNA in a sequence-specific manner. Barley stripe mosaic virus (BSMV) is an established VIGS vector for barley and wheat; however, silencing using this vector is generally transient, with efficient silencing often being confined to the first two or three systemically infected leaves. To investigate this further, part of the barley Phytoene desaturase (PDS) gene was inserted into BSMV and the resulting photobleaching in infected barley plants was used as a reporter for silencing. In addition, downregulation of PDS mRNA was measured by quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR). Using fragments of PDS ranging from 128 to 584 nucleotides in BSMV, we observed that insert length influenced stability but not efficiency of VIGS. Silencing was transient in most cases; however, the decrease in PDS mRNA levels measured by qRT-PCR began earlier and lasted longer than the photobleaching. Occasionally, silencing persisted and could be transmitted through seed as well as via mechanical inoculation, although large parts of the insert had been lost from the virus vector. The instability of the insert, observed consistently throughout our experiments, offers an explanation for the transient nature of silencing when using BSMV as a VIGS vector.
Genome-Wide Transcript Analysis of Bradyrhizobium japonicum Bacteroids in Soybean Root Nodules
Authors: Pessi Gabriella , Ahrens Christian H. , Rehrauer Hubert , Lindemann Andrea , Hauser Felix , Fischer Hans-Martin , Hennecke Hauke
Published: October 2007

The transcriptome of endosymbiotic Bradyrhizobium japonicum bacteroids was assessed, using RNA extracted from determinate soybean root nodules. Results were compared with the transcript profiles of B. japonicum cells grown in either aerobic or microaerobic culture. Microoxia is a known trigger for the induction of symbiotically relevant genes. In fact, one third of the genes induced in bacteroids at day 21 after inoculation are congruent with those up-regulated in culture by a decreased oxygen concentration. The other induced genes, however, may be regulated by cues other than oxygen limitation. Both groups of genes provide a rich source for the possible discovery of novel functions related to symbiosis. Samples taken at different timepoints in nodule development have led to the distinction of genes expressed early and late in bacteroids. The experimental approach applied here is also useful for B. japonicum mutant analyses. As an example, we compared the transcriptome of wild-type bacteroids with that of bacteroids formed by a mutant defective in the RNA polymerase transcription factor σ54. This led to a collection of hitherto unrecognized B. japonicum genes potentially transcribed in planta in a σ54-dependent manner.
Basal Resistance AgainstPseudomonas syringaeinArabidopsisInvolves WRKY53 and a Protein with Homology to a Nematode Resistance Protein
Authors: Murray Shane L. , Ingle Robert A. , Petersen Lindsay N. , Denby Katherine J.
Published: October 2007

Basal resistance is the ultimately unsuccessful plant defense response to infection with a virulent pathogen. It is thought to be triggered by host recognition of pathogen-associated molecular patterns, with subsequent suppression of particular components by pathogen effectors. To identify novel components of Arabidopsis basal resistance against the bacterial pathogen Pseudomonas syringae pv. tomato, microarray expression profiling was carried out on the cir1 mutant, which displays enhanced resistance against P. syringae pv. tomato. This identified two genes, At4g23810 and At2g40000, encoding the transcription factor WRKY53 and the nematode resistance protein-like HSPRO2, whose expression was upregulated in cir1 prior to pathogen infection and in wild-type plants after P. syringae pv. tomato infection. WRKY53 and HSPRO2 are positive regulators of basal resistance. Knockout mutants of both genes were more susceptible to P. syringae pv. tomato infection than complemented lines, with increased growth of the pathogen in planta. WRKY53 and HSPRO2 appear to function downstream of salicylic acid and to be negatively regulated by signaling through jasmonic acid and ethylene.
Induction of p-Coumaroyldopamine and Feruloyldopamine, Two Novel Metabolites, in Tomato by the Bacterial Pathogen Pseudomonas syringae
Authors: Zacarés Laura , López-Gresa María Pilar , Fayos Joaquín , Primo Jaime , Bellés José María , Conejero Vicente
Published: October 2007

Inoculation of tomato plants (Solanum lycopersicum cv. Rutgers) with Pseudomonas syringae pv. tomato led to the production of a hypersensitive-like response in this pathovar of tomato. Accumulation of hydroxycinnamic acid amides (HCAA) of tyramine (p-coumaroyltyramine and feruloyltyramine) and dopamine (p-coumaroyldopamine and feruloyldopamine) was detected after bacterial infection. Two of them, p-coumaroyldopamine and feruloyldopamine, are described for the first time. The accumulation of HCAA was preceded by an increment of hydroxycinnamoyl-CoA:tyramine N-hydroxycinnamoyl transferase (THT) gene expression. HCAA also accumulated in transgenic NahG tomato plants overexpressing a bacterial salicylic hydroxylase. However, treatment of plants with the ethylene biosynthesis inhibitor, aminoethoxyvinilglycine, led to a reduction in the accumulation of THT transcripts and HCAA. Together, the results suggest that pathogen-induced induction of ethylene is essential for HCAA synthesis, whereas salicylic acid is not required for this response. In addition, notable antibacterial and antioxidant activities were found for the new HCAA, thus indicating that they could play a role in the defense of tomato plants against bacterial infection.
The TIR-NB-LRR Gene SNC1 Is Regulated at the Transcript Level by Multiple Factors
Authors: Li Yongqing , Yang Shuhua , Yang Huijun , Hua Jian
Published: October 2007

SNC1 (suppressor of NPR1, constitutive 1) is a haplotype-specific Toll and interleukin-1 receptor-like nucleotide-binding site leucine-rich repeat type of resistance (R)-like gene possibly mediating race-specific disease resistance. Inactivation of its negative regulator BON1 (BONZAI1)/CPN1 and BAP1 genes or upregulation of its expression epigenetically lead to constitutive defense responses and dwarf phenotype. Here, we report an autoactivation of SNC1 by introducing it into Arabidopsis as a transgene. The SNC1 genomic fragment confers a dwarf phenotype induced by defense response upregulation associated with a higher SNC1 transcript level. Analysis of the β-glucuronidase reporter gene under the control of the SNC1 promoter suggests three modes of regulation on the SNC1 transcript level: a repression by the chromosomal structure, a feedback amplification from SNC1 on its promoter sequences, and a repression by BON1. These regulations appear to be independent of each other. The regulation of SNC1 possibly exemplifies a universally complex control of R genes to ensure a repression of R activation under nonstress conditions and a robust activation of defense responses once the R gene is induced.
Genetic Diversity of Lettuce for Resistance to Bacterial Leaf Spot Caused by Xanthomonas campestris pv. vitians
Authors: Bull Carolee T. , Goldman Polly H. , Hayes Ryan , Madden Laurence V. , Koike Steven T. , Ryder Ed
Published: October 2007

Lettuce plants were artificially inoculated with three isolates of Xanthomonas campestris pv. vitians in field and greenhouse evaluations for genetic variation in resistance to bacterial leaf spot. The cultivar Little Gem had the least amount of disease, whether evaluated for disease severity or disease incidence. Disease severity levels for cultivar Batavia Reine des Glaces were not significantly different from those of Little Gem. Several cultivars including Vista Verde, Pybas 251, Pacific, Clemente, Salinas 88, and Sniper were highly susceptible. There was a strong correlation between results obtained in the greenhouse and those obtained in the field (r = 0.77, P = 0.009) indicating that greenhouse assays may be used to increase the number of cultivars evaluated and to speed breeding efforts.

Accepted for publication 17 May 2007. Published 17 September 2007.
Low concentrations of doxorubicin sensitizes human solid cancer cells to tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL)‐receptor (R) 2‐mediated apoptosis by inducing TRAIL‐R2 expression
Authors: Wu Xiu‐Xian , Jin Xing‐Hua , Zeng Yu , El Hamed Ahmed Mamdouh Abd , Kakehi Yoshiyuki
Published: October 2007

There is accumulating evidence suggesting that tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL)‐receptor (R) 2 is a promising molecular target for cancer therapy. Therefore, we investigated the effect of chemotherapeutic agents on TRAIL‐R2‐mediated apoptosis and cytotoxicity in various human solid cancer cells. Treatment of the ACHN human renal cell carcinoma (RCC) cell line with agonistic TRAIL‐R2 antibody (lexatumumab) in combination with 5‐fluorouracil, vinblastine, paclitaxel, or docetaxel did not overcome resistance to these agents. However, treatment with lexatumumab in combination with doxorubicin had a synergistic cytotoxicity. Synergy was also achieved in two other human RCC cell lines, Caki‐1 and Caki‐2, and in eight primary RCC cell cultures. Sequential treatment with doxorubicin followed by lexatumumab induced significantly more cytotoxicity than reverse treatment or simultaneous treatment. Low concentrations of doxorubicin (0.1 and 1 µg/mL) significantly increased TRAIL‐R2 expression at both the mRNA and protein levels. Furthermore, the combination of doxorubicin and lexatumumab significantly enhanced caspase 8 activity, Bid cleavage, Bcl‐xL decrease, release of cytochrome c, and caspase 9 and caspase 3 activity, and induced synergistic apoptosis. The activation of caspases and apoptosis induced with lexatumumab and doxorubicin was blocked by the human recombinant DR5:Fc chimeric protein. In addition, synergistic cytotoxicity was also observed in human prostate, bladder, and lung cancer cells, but was inhibited by the DR5:Fc chimeric protein. These findings suggest that doxorubicin sensitizes solid cancer cells to TRAIL‐R2‐mediated apoptosis by inducing TRAIL‐R2 expression, and that the combination treatment with lexatumumab and doxorubicin might be a promising targeted therapy for cancers, including RCC, prostate, bladder, and lung cancers. (Cancer Sci 2007; 98: 1969–1976)
Selected new antithrombotic agents and neuraxial anaesthesia for major orthopaedic surgery: management strategies
Authors: Rosencher N. , Bonnet M.‐P. , Sessler D. I.
Published: October 2007

We propose recommendations to reduce the risk of haemorrhagic events associated with regional anaesthesia in patients treated with newer anticoagulants after orthopaedic surgery. The risk/benefit ratio should be individualised for each patient according to the type and dose of anticoagulant, the type of regional anaesthesia and patient risk factors. Neuraxial anaesthetic management strategy can be based on the pharmacokinetic properties of specific anticoagulants, including the time required to reach maximal concentration, half‐life, and dose regimen. Central neuraxial blocks should not be performed and epidural catheters should not be removed until at least two half‐lives after the last injection of anticoagulant, the half‐life depending on renal function. After removing a catheter or after a haemorrhagic puncture, the timing of the next anticoagulant injection should be based on the time required for an anticoagulant dose to reach maximum activity. Vigilance remains paramount during the initial days after removal of a neuraxial catheter.
A prospective randomised double blind study to evaluate the effect of peribulbar block or topical application of local anaesthesia combined with general anaesthesia on intra‐operative and postoperative complications during paediatric strabismus surgery
Authors: Gupta N. , Kumar R. , Kumar S. , Sehgal R. , Sharma K. R.
Published: October 2007

We studied 45 ASA I/II children aged between 2 and 13 years scheduled for elective strabismus surgery, randomly allocated to receive either a peribulbar block or topical lidocaine 2% combined with general anaesthesia, or general anaesthesia alone. The incidence and severity of the occulocardiac reflex, the requirement for atropine, the occurrence of arrhythmias and incidence of postoperative nausea and vomiting following surgery at 1, 2 and 4 h were studied. We found the incidence and severity of occulocardiac reflex intra‐operatively was significantly reduced in children who received a peribulbar block. The incidence of postoperative nausea and vomiting was significantly reduced in patients receiving either peribulbar block or topical local anaesthesia combined with general anaesthesia, compared to general anaesthesia alone (p = 0.008).
The effect of time of day on the duration of neuromuscular blockade elicited by rocuronium*
Authors: Cheeseman J. F. , Merry A. F. , Pawley M. D. M. , De Souza R. L. , Warman G. R.
Published: October 2007

In a prospective, observational trial, we investigated the influence of time of day on the duration of neuromuscular blockade (NMB) elicited by rocuronium. Forty‐nine patients scheduled for surgery between 08:00 and 02:00 were enrolled after giving written informed consent. Time to neuromuscular recovery was measured following three doses: (1) a fat‐free‐mass (FFM) related induction dose (0.6 mg.kg−1: n = 47); (2) a maintenance dose (20% of the induction dose: n = 42); and (3) a standard 10‐mg dose (n = 35). The extent of NMB was dependent on the time of administration (p = 0.038 General Linear Model Analysis). The maximum effect of 50 min (95% CI 41–59 min) was elicited between 08:00 and 11:00 and the minimum duration of 29 min (95% CI 23–35 min) between 14:00 and 17:00 (p = 0.005). A similar pattern was observed for the maintenance dose. The duration of action of rocuronium is influenced by time of day and this effect is of potential clinical significance and practical relevance to research.
Improving the efficiency of the drawover anaesthetic breathing system
Authors: Eales M. , Rowe P. , Tully R.
Published: October 2007

We investigated modifications to the reservoir tube usually used in drawover anaesthetic breathing systems as a method of improving its efficiency and performance. The resulting oxygen concentration was recorded at different oxygen flow rates whilst an artificial lung was being ventilated over a range of minute volumes. Addition of a reservoir bag and valves significantly increased the measured percentage of oxygen at the common gas outlet when compared to a 300‐ml reservoir tube. There was no difference in the percentage of oxygen when comparing a reservoir bag and a 600‐ml reservoir tube.
Effects of continuous remifentanil administration on intra‐operative subcutaneous tissue oxygen tension
Authors: Kabon B. , Kugener A. , Gruenberger T. , Niedermayr M. , Fleischmann E. , Freissmuth M. , Kurz A.
Published: October 2007

Surgical stress response markedly increases sympathetic nerve activity and catecholamine concentrations. This may contribute to peripheral vasoconstriction, reduced wound perfusion and subsequent tissue hypoxia. Opioids are known to depress the hypothalamic‐adrenal response to surgery in a dose‐dependent manner. We tested the hypothesis that continuous remifentanil administration produces improved subcutaneous tissue oxygen tension compared to fentanyl bolus administration. Forty‐six patients undergoing major abdominal surgery were randomly assigned to receive either fentanyl bolus administration or continuous remifentanil infusion. Mean subcutaneous tissue oxygen values over the entire intra‐operative period were significantly higher in the remifentanil group, when compared to the fentanyl group: 8 (2) kPa vs 6.7 (1.5) kPa, % CI difference: − 2.3 kPa to − 0.3 kPa, p = 0.013. Continuous intra‐operative opioid administration may blunt vasoconstriction caused by surgical stress and adrenergic responses more than an equi‐effective anaesthetic regimen based on smaller‐dose bolus opioid administration.
Relative lung deposition of salbutamol following inhalation from a spacer and a Sidestream jet nebulizer following an acute exacerbation
Authors: Mazhar Syed H. R. , Ismail Nahlah E. , Newton Duncan A. G. , Chrystyn Henry
Published: October 2007

What is already known about this subject

• Studies have shown that a large volume spacer attached to a metered dose inhaler provides similar bronchodilator effects to nebulized dosing during the management of patients following an acute exacerbation.

• Due to the high doses used, these effects could be measured at the top of the dose–response relationship and the response limited due to the patient's exacerbation.

• Although clinical end‐points are the gold standard to show comparability, some indication of similar lung deposition is useful to consolidate any claims.

What this study adds

• The urinary pharmacokinetic method we have used postinhalation provides an index of lung deposition for inhalation methods that can be incorporated into the routine management of patients with an acute exacerbation.

• This is the first study to identify and compare lung deposition and systemic delivery for inhalation methods within the setting of the routine management of asthma and chronic obstructive pulmonary disease patients following hospitalization due to an acute exacerbation.

• The study highlights the comparability of the doses for the two inhalation methods evaluated with respect to lung deposition, systemic delivery and bronchodilator response.

Background

Studies comparing inhalation methods in acute exacerbations have not assessed lung deposition.

Methods

Five 100‐μg salbutamol doses were inhaled from a metered dose inhaler plus spacer (MDI + SP) and 5 mg was nebulized (NEB) following acute exacerbation hospitalization. Urinary salbutamol excretion was determined at 30 min (USAL0.5) and over 24 h (USAL24) postinhalation together with forced expiratory volume in 1 s (FEV1).

Results

The USAL0.5 mean ratio (90% confidence interval) post MDI + SP and NEB [n = 19 asthma, 11 chronic obstructive pulmonary disease (COPD)] was 1.01 (0.81, 1.26). USAL24 was less (P < 0.001) following MDI + SP, whereas FEV1 was similar. Only a small difference between asthmatics and COPD patients was observed for the MDI + SP in that the USAL0.5 was higher in the asthmatics for the spacer method.

Conclusion

The relative lung deposition after inhaling 500 μg salbutamol from MDI + SP is similar to 5 mg from a Sidestream nebulizer following an acute exacerbation.
Perforated peptic ulcer and short‐term mortality among tramadol users
Authors: Tørring Marie L. , Riis Anders , Christensen Steffen , Thomsen Reimar W. , Jepsen Peter , Søndergaard Jens , Sørensen Henrik T.
Published: October 2007

What is already known about this subject

• Use of nonsteroidal anti‐inflammatory drugs (NSAIDs) is a strong risk and prognostic factor for peptic ulcer perforation, and alternative analgesics are needed for high‐risk patients.

• Pain management guidelines propose tramadol as a treatment option for mild‐to‐moderate pain in patients at high risk of gastrointestinal side‐effects, including peptic ulcer disease.

• Tramadol may mask symptoms of peptic ulcer complications, yet tramadol's effect on peptic ulcer prognosis is unknown.

What this study adds

• In this population‐based study of 1271 patients hospitalized with peptic ulcer perforation, tramadol appeared to increase mortality at least as much as NSAIDs.

• Among users of tramadol, alone or in combination with NSAIDs, adjusted 30‐day mortality rate ratios were 2.02 [95% confidence interval (CI) 1.17, 3.48] and 1.32 (95% CI 0.89, 1.95), compared with patients who used neither tramadol nor NSAIDs.

Aim

Use of nonsteroidal anti‐inflammatory drugs (NSAIDs) increases risk and worsens prognosis for patients with complicated peptic ulcer disease. Therefore, patients who are at high risk of peptic ulcer often use tramadol instead of NSAIDs. Tramadol's effect on peptic ulcer prognosis is unknown. The aim was to examine mortality in the 30 days following hospitalization for perforated peptic ulcer among tramadol and NSAID users compared with non‐users.

Methods

The study was based on data on reimbursed prescriptions and hospital discharge diagnoses for the 1993–2004 period, extracted from population‐based healthcare databases. All patients with a first‐time diagnosis of perforated peptic ulcer were identified, excluding those with previous ulcer diagnoses or antiulcer drug use. Cox regression was used to estimate 30‐day mortality rate ratios for tramadol and NSAID users compared with non‐users, adjusting for use of other drugs and comorbidity.

Results

Of 1271 patients with perforated peptic ulcers included in the study, 2.4% used tramadol only, 38.9% used NSAIDs and 7.9% used both. Thirty‐day mortality was 28.7% overall and 48.4% among users of tramadol alone. Compared with the 645 patients who used neither tramadol nor NSAIDs, the adjusted mortality rate in the 30 days following hospitalization was 2.02‐fold [95% confidence interval (CI) 1.17, 3.48] higher for the 31 ‘tramadol only’ users, 1.41‐fold (95% CI 1.12, 1.78) higher for the 495 NSAID users and 1.32‐fold (95% CI 0.89, 1.95) higher for the 100 patients who used both drugs.

Conclusion

Among patients hospitalized for perforated peptic ulcer, tramadol appears to increase mortality at a level comparable to NSAIDs.