bluuebunny/crossref_metadata_2025_split huggingface dataset:
End of life vehicle management in areas of low technology sophistication. A case study in Greece
Authors: Sakkas N. , Manios T. 
Published: September 2003

AbstractThis paper was based on the findings of a study aimed at identifying and evaluating appropriate investment strategies in the area of end of life vehicle management (ELVM), especially against the emerging policy framework, as outlined by the recent EU legislation (2000/53 EG directive). The study was carried out for OMPM SA (Organisation for the Management of Public Material), a Greek organization, with many years' involvement in the management of ELVs. The departure point of the work was the critical review of available best practices, mostly compiled by means of a considerable number of on the spot visits to diverse ELVM processing facilities in the Northern EU. These experiences and practices were critically adapted to the very different local circumstances, characterized by an underdeveloped market and a low operational sophistication. In this way, the recommendations of the study, also reported in this work, are of a wider relevance to areas where the main priority is rather the development and rationalization of the ELVM business itself, before getting on to the subtler fine tuning and optimization issues that may be on the agenda in more mature environments. Copyright © 2003 John Wiley & Sons, Ltd and ERP Environment.
Environmental reporting within the forest and paper industry
Authors: Sinclair Penny , Walton Julia 
Published: September 2003

AbstractResearch on environmental reporting within individual sectors and industries is limited. Generic studies have typically focused on the reporting practices of the world's largest corporates. Some industries and sectors are under‐represented within these studies, limiting the potential for industry‐ or sector‐specific analysis. Forest and paper is one industry frequently under‐represented.
This study examines environmental reporting amongst the top 100 forest and paper companies. The scale of environmental report publication is investigated, and the breadth and depth of reporting on the key industry issues of forest management and fibre procurement examined. The results show reporting is more prevalent amongst larger corporates but marked regional variations are evident. Most noticeably, Scandinavian companies are reporting more extensively, both in terms of the number of levels at which they report and the depth of information included on forest management and fibre procurement. Reasons for the marked regional variations in reporting are considered and markets for forest products and preferences within those markets for specific certification schemes identified as potential influencing factors. Copyright © 2003 John Wiley & Sons, Ltd and ERP Environment.
Isolation of mast cell secretory lysosomes using flow cytometry
Authors: Rajotte Daniel , Stearns Carol D. , Kabcenell Alisa K. 
Published: September 2003

AbstractBackgroundMast cells are specialized secretory cells of the immune system. Through exocytosis of their secretory lysosomes and secretory granules, mast cells release biologically active substances such as histamine and proteases. Mast cell secretory granules have been studied extensively but much less attention has been given to secretory lysosomes. Studies on mast cell secretory lysosomes are limited by the lack of selective markers and the difficulty to isolate this organelle from conventional lysosomes. Our goal was to develop better tools to study secretory lysosomes.MethodsWe engineered a rat mast cell line over expressing a rat mast cell protease (RMCP) tagged with a red fluorescent protein (RMCP‐DsRed). We used single organelle flow analysis (SOFA) to detect fluorescently labeled secretory lysosomes. The labeled organelles were then sorted using the fluorescence‐assisted organelle sorting (FAOS) method.ResultsWe show that the RMCP‐DsRed fusion protein selectively localizes to the lysosomal compartment and is exocytosed upon activation, confirming its localization in secretory lysosomes. Lysosomal fractions from cells expressing the RMCP‐DsRed fusion were analyzed by SOFA and a specific population of secretory lysosome was identified. Finally, we sorted secretory lysosomes and showed that the sorted material had a higher specific activity for the compartment marker hexosaminidase than a sample obtained by conventional methods.ConclusionsOur work further demonstrates the usefulness of flow cytometry to study cellular organelles, and provides new tools to better understand the physiology of secretory lysosomes. Cytometry Part A 55A:94–101, 2003. © 2003 Wiley‐Liss, Inc.
Cytometric analysis of protein expression and apoptosis in human primary cells with a novel microfluidic chip‐based system
Authors: Chan Samuel D. H. , Luedke Gerd , Valer Marc , Buhlmann Carsten , Preckel Tobias 
Published: September 2003

AbstractBackgroundWork with primary cells is inherently limited by source availability and life span in culture. Flow cytometry offers extensive analytical opportunities but generally requires high cell numbers for an experiment.MethodsWe have developed assays on a microfluidic system, which allow flow cytometric analysis of apoptosis and protein expression with a minimum number of fluorescently stained primary cells. In this setup, the cells are moved by pressure‐driven flow inside a network of microfluidic channels and are analyzed individually by two‐channel fluorescence detection. For some assays the staining reactions can be performed on‐chip and the analysis is done without further washing steps.ResultsWe have successfully applied the assays to evaluate (a) activation of E‐selectin (CD62E) expression by interleukin‐1β in human umbilical vein endothelial cells (HUVECs), (b) induction of CD3 by phorbol‐12‐myristate‐13‐acetate in freshly prepared human peripheral blood lymphocytes, and (c) staurosporine‐induced apoptosis in HUVEC and normal human dermal fibroblasts.ConclusionsResults obtained with the microfluidic system are in good correlation with data obtained using a standard flow cytometer, but demonstrate new dimensions in low reagent and cell consumption. Cytometry Part A 55A:119–125, 2003. © 2003 Wiley‐Liss, Inc.
Quantification of stretch‐induced cytoskeletal remodeling in vascular endothelial cells by image processing
Authors: Yoshigi Masaaki , Clark Edward B. , Yost H. Joseph 
Published: September 2003

AbstractBackgroundReorientation of the cell axis induced by cyclic stretching is an early response to mechanical forces in vitro. However, quantitative assay for this phenomenon has been difficult due to lack of robust methods. We hypothesized that cell orientation may be redefined by the orientation of actin fibers. We developed image processing methods to quantitate the orientation and density of actin fibers.MethodsA convolution filter using Sobel kernels was adapted to determine the orientation and density of actin fibers in human endothelial cells. Unidirectional stretching (10%, 0.5 Hz) was applied to induce cytoskeletal remodeling by varying the duration of stimulation (control, 0.5, 1, 2, 5, 10, and 20 h). Actin fibers were visualized by fluorescent phalloidin. The image processing method was compared with the manual method for reproducibility. Both confluent and subconfluent cells were tested to assess the efficacy of the methods.ResultsCyclic stretch‐induced dense and uninterrupted actin cabling formed across the cell body and, later, the actin fibers became aligned perpendicular to the stretch direction. The variance of actin fiber orientation became smaller after 2 h of stretch (F < 0.01). The actin fiber density index, a derived parameter related to the density of actin fibers, increased as early as 30 min of stretching (P < 0.05) and decreased after 10 h of stretching. Reproducibility of our method was extremely good. Applicability of the method was not compromised by cell density.ConclusionsOur method is reliable for quantifying cytoskeletal remodeling induced by mechanical force. Cytometry Part A 55A:109–118, 2003. © 2003 Wiley‐Liss, Inc.
Early detection of apoptosis by staining of acid‐treated apoptotic cells with FITC‐labeled lectin from Narcissus pseudonarcissus
Authors: Heyder Petra , Gaipl Udo S. , Beyer Thomas D. , Voll Reinhard E. , Kern Peter M. , Stach Christian , Kalden Joachim R. , Herrmann Martin 
Published: September 2003

AbstractBackgroundExposure of anionic phospholipids and modified carbohydrates are main parts of the apoptotic death program. Cells undergoing apoptosis can be identified by various methods, detecting surface changes or modifications of their organelles, respectively. We describe a method for the detection of early apoptosis by staining of cells with fluorescein isothiocyanate (FITC)–labeled lectin from Narcissus pseudonarcissus (NPn).MethodsApoptosis in cells or in cell lines was induced by various stimuli. To detect apoptosis the cells were stained with FITC‐labeled lectin of NPn. After a short‐term acid treatment they were analyzed by flow cytometry.ResultsThe instability of the cytoplasmic membrane against acid and the binding of NPn were very early features of apoptotic cell death. The NPn lectin staining procedure detected apoptosis with high sensitivity. The staining was stable for at least 12 h.ConclusionsThe method described in this study is suitable for the detection of the very early phases of apoptosis. The NPn lectin staining after short‐term acid treatment can, therefore, be added to the list of reliable tools for the research of cell death. Cytometry Part A 55A:86–93, 2003. © 2003 Wiley‐Liss, Inc.
Pharmacogenomics of schizophrenia: Towards personalized psychiatry
Authors: Gurwitz David 
Published: September 2003

AbstractPsychiatry is among the primary medical disciplines to focus on the potential benefits from the cloning of the human genome and the subsequent implementation of personalized medicine. This viewpoint reflects the evident difficulties of current psychiatric practice compared with other disciplines, most notably the limited understanding of disease etiologies, the lack of reliable and objective diagnostic tools, and the paucity of relevant animal models. These aspects of psychiatry face major changes as a consequence of the recent identification of several schizophrenia risk genes. The reviews presented in this issue illustrate the potential for innovative drug discovery and personalized pharmacotherapy for schizophrenia. Drug Dev. Res. 60:71–74, 2003. © 2003 Wiley‐Liss, Inc.
Overview: Towards individualized treatment in schizophrenia
Authors: Müller Daniel J. , De Luca Vincenzo , Kennedy James L. 
Published: September 2003

AbstractSchizophrenia is a serious mental disorder involving distortions of thinking or perception, inappropriate or blunted affect, and cognitive deficits may evolve in the course of time. Antipsychotics are the first choice for treatment; however, interindividual variability in response and side effects are commonly observed. To avoid time‐consuming, cost‐intensive, and potentially hazardous drug treatments, clinicians should ideally anticipate which antipsychotic is the most effective and less harmful for a given patient. This form of “individualised treatment” can only succeed if specific characteristics are identified as highly associated with the favourable response. Demographical, clinical, or physiological characteristics by themselves have not been shown to predict antipsychotic drug response to a clinically meaningful extent. As genetic factors are likely to contribute substantially to the efficacy and toxicity of drugs, numerous pharmacogenetic studies have searched for associations between gene variants and antipsychotic drug response. The first generation of pharmacogenetic studies yielded mainly negative and often inconsistent findings that are most likely the result of substantial heterogeneity among studies generally using small samples. Perhaps the most robust associations were found between polymorphisms of the serotonin 2A or the dopamine 2 receptor genes with response to clozapine or conventional antipsychotics, respectively. However, effect sizes are rather small and, therefore, further research is needed that integrates recent advances in genomics, proteomics, and biostatistics. Nonetheless, these findings are consistent with the dopamine/serotonin hypothesis in schizophrenia. The continuous discovery of new gene variants and progressive methodological improvements will help elucidate the molecular pathological mechanisms in schizophrenia, and reveal new avenues for drug development research. Drug Dev. Res. 60:75–94, 2003. © 2003 Wiley‐Liss, Inc.
Pharmacogenomics and animal models of schizophrenia
Authors: Klink Ruby , Boksa Patricia , Joober Ridha 
Published: September 2003

AbstractSchizophrenia is a syndromal brain disease of largely unknown pathophysiology and most likely heterogeneous etiology in which genetic predisposition constitutes the major risk factor. In recent years, a shift from a monolithic view of the disorder is leading to its dissection into component phenotypic modules or endophenotypes that may differ in pathophysiology, underlying genetic diathesis, or treatment response. Reducing phenotypic heterogeneity by focusing on endophenotypes will facilitate the production of valid animal models to be used in experimental approaches, improve our chances of uncovering genes predisposing to the disease in linkage or association approaches, and simplify generation of novel molecular targets for the drug discovery process. We hereby review some recently generated mouse models that replicate specific endophenotypes observed in schizophrenia and that implicate putative contributing genes that may be exploited to explore novel drug targets. These are derived from opposing but complementary perspectives. One approach developed in our work begins with mouse models of schizophrenia traits to uncover candidate schizophrenia genes. Another approach followed by several other groups begins with putative schizophrenia vulnerability genes to investigate the corresponding endophenotype in mouse models. Combined with global analysis of gene expression, these mouse models offer the hope that the disease‐causing and treatment pathways implicated in schizophrenia will finally be unraveled. Drug Dev. Res. 60:95–103, 2003. © 2003 Wiley‐Liss, Inc.
Pharmacogenetic and pharmacogenomic research for the prediction of response to antipsychotics in schizophrenia
Authors: Arranz M.J. , Kerwin R.W. 
Published: September 2003

AbstractTreatment of schizophrenia sufferers requires the use of antipsychotic drugs. First developed in the 1950s, two major types of antipsychotics are currently available: classical or conventional antipsychotics and atypical antipsychotics. Selection of treatment is based on trial and error strategies with a detrimental effect on patients' prognosis and chances of recovery. Clinical and genetic indicators have been investigated as predictors of response to antipsychotic treatment. Several studies have reported association between clinical observations and treatment outcome. However, clinical indicators require post‐treatment information that may delay selection of a beneficial drug. Alternatively, genetic polymorphisms have been suggested as useful pre‐treatment predictors. In the last decade, pharmacogenetic researchers have reported numerous associations between antipsychotic response and polymorphisms in genes coding for drug‐targeted receptors and metabolic enzymes. This research has provided information that can be used for the individual prediction of response to specific antipsychotics. Much more is expected from the surge of pharmacogenomic research in pharmaceutical companies. Novel targets for antipsychotic treatment, improved and safer drugs, and individualised treatment are some of the goals expected to achieve in the near future. Drug Dev. Res. 60:104–110, 2003. © 2003 Wiley‐Liss, Inc.
Toward schizophrenia genes: Genetics and transcriptome
Authors: Ito Chihiro , Ouchi Yuta 
Published: September 2003

AbstractSchizophrenia is highly heritable, and the identification of its genetic factors is receiving great attention. In this review, we digested current genetic findings about schizophrenia. At first, DISC‐1 and ‐2 derived from a large Scottish family, and velo‐cardio‐facial syndrome caused by microdeletion of 22q11, are hot topics in cytogenic studies. Secondly, selections and classifications of samples become the biggest problems in linkage studies, because many following studies failed to confirm replicated linkages. Thirdly, a lot of functional and/or positional candidate genes are analyzed. Some genes, including NRG1, DTNBP1, G72, DAAO, RGS4, and PRODH2, are recently identified in association studies. In the last method, the novel way to select functional candidate genes with a transcriptome analysis is getting presented. The transcriptome analysis makes it possible to identify up‐ and down‐regulated genes from overall transcriptions (mRNAs). We also have an ongoing case‐control study about schizophrenia, following serial analysis of gene expression (SAGE), one of the transcriptome analyses. We analyzed changes of gene expressions in methamphetamine‐ and phencyclidine‐treated rodent cerebral cortexes, two well‐known animal models of schizophrenia. We identified their homologous 209 human genes as candidates. These findings will bring us new understanding of pathophysiologic aspects and further drug targets toward schizophrenia. Drug Dev. Res. 60:111–118, 2003. © 2003 Wiley‐Liss, Inc.
Genetic perspectives of histamine and muscarinic receptors in schizophrenia and clozapine response
Authors: Mancama Dalu , Arranz Maria J. , Kerwin Robert W. 
Published: September 2003

AbstractThe mechanisms that underlie schizophrenia and influence outcome to antipsychotic treatment are unclear, and remain the focus of intense investigation. Genetic studies have been at the forefront of work to delineate the disorders aetiology and have led to the identification of gene variants, predominantly throughout neurotransmitter pathways, that may be important. Prevailing evidence, however, suggests that those variants so far identified confer a relatively limited influence, and in the search to identify the further participants growing evidence has emerged implicating the involvement of histamine and muscarinic receptor pathways. Studies investigating the genetic contribution of these systems in the disorder are relatively nascent, and consequently the extent to which each may be involved is presently unclear. Further work is, therefore, warranted to determine this role, since these pathways potentially offer an unprecedented insight into the disorders aetiology. It is envisaged this knowledge may also contribute to clarifying the mechanisms that moderate antipsychotic efficacy, and could accelerate ongoing efforts to develop new therapies and predictive pharmacogenetic approaches associated with this area of drug treatment. Drug Dev. Res. 60:119–126, 2003. © 2003 Wiley‐Liss, Inc.
Consequences of low levels of nicotinic acetylcholine receptors in schizophrenia for drug development
Authors: Leonard Sherry 
Published: September 2003

AbstractThe incidence of smoking in the mentally ill is much higher than in the general population and is inordinately high in schizophrenia. It has been suggested that this might be an attempt to self‐medicate an underlying biological deficit. The receptors that mediate nicotinic responses are decreased in many regions of postmortem brain in schizophrenic smokers, compared to control smokers. Patients exhibit differential responses to nicotine in a number of behavioral, cognitive, and metabolic measures. As nicotine regulates the release of a large number of neurotransmitters, it is likely that differences in down‐stream neuroadaptation of other transmitter/receptor systems would result from the reduced level of nicotinic receptors in these patients. The disparate responses to nicotine have consequences for the development of cholinergic drug therapies in schizophrenia. Drug Dev. Res. 60:127–136, 2003. © 2003 Wiley‐Liss, Inc.
Glutamate receptor genes as candidates for schizophrenia susceptibility
Authors: Fukumaki Yasuyuki , Shibata Hiroki 
Published: September 2003

AbstractThe glutamatergic dysfunction hypothesis suggests that genes involved in the glutamate neurotransmitter system are candidates for schizophrenia‐susceptibility genes. We have been doing systematic studies of the association of schizophrenia with each member of the glutamate receptor gene family. In this review, we summarize our results of association studies of five glutamate receptor genes, two of which are metabotropic, GRM2 and GRM3, whereas the other four are ionotropic, GRIA4, GRIK1, GRIK2 and GRIN1. Haplotype analyses using combinations of SNPs evenly distributed across the relevant genes showed significant associations of GRM3 and GRIA4 with schizophrenia. We discuss the possible involvement of glutamate receptor genes in the pathogenesis of schizophrenia, on the basis of association as well as linkage and postmortem studies previously reported. Replication of positive associations using different populations and the family‐based study are necessary to confirm the results. Generation of gene‐manipulated mice to represent endophenotypes of schizophrenia would be an alternative way to verify susceptibility genes. Some members of the glutamate receptor family may be promising targets for schizophrenia drugs. Drug Dev. Res. 60:137–151, 2003. © 2003 Wiley‐Liss, Inc.
Pharmacogenetics and association studies in schizophrenia
Authors: Ntzani Evangelia E. , Ioannidis John P. A. 
Published: September 2003

AbstractWe present an overview of the contribution of genetic association studies on understanding schizophrenia pharmacogenomics. Using a MEDLINE search (March 2003), we identified 96 reports on genetic associations of diverse polymorphisms with response to therapy or adverse events from antipsychotics. Most studies have targeted polymorphisms in the cytochrome p450 metabolizing gene system, the dopamine receptor genes, and the serotonin receptors and serotonin transporter genes, but an increasing number of new gene targets is added continuously. We could identify more than 2 published reports only for 16 pharmacogenetic associations, and only 10 of them have had more than 3 published reports. Most of these studies have had small sample size and none recruited >1,000 patients with schizophrenia. Sample size exceeded 600 patients in 3 reports by the same team and no significant association has been found in these reports for 9 distinct polymorphisms of the DRD2 gene, two polymorphisms of the serotonin transporter gene, or the 48‐bp VNTR polymorphism of the DRD4 gene. Meta‐analyses of the 102‐T/C and the His452Tyr polymorphisms of the HTR2A gene and of the Ser9Gly polymorphism of the DRD3 gene suggest a significant association with therapeutic response that is, nevertheless, no longer formally statistically significant when the first, hypothesis‐generating study is excluded. Genetic association studies are a valuable tool in schizophrenia pharmacogenetic research. However, large, carefully conducted studies with appropriately defined analysis and outcomes and full reporting, as well as validation of associations across several studies, are essential for creating a rational knowledge base in this field. Drug Dev. Res. 60:152–163, 2003. © 2003 Wiley‐Liss, Inc.