bluuebunny/crossref_metadata_2025_split huggingface dataset:
The WAVE2/Abi1 complex differentially regulates megakaryocyte development and spreading: implications for platelet biogenesis and spreading machinery
Authors: Eto Koji , Nishikii Hidekazu , Ogaeri Takunori , Suetsugu Shiro , Kamiya Akihide , Kobayashi Toshihiro , Yamazaki Daisuke , Oda Atsushi , Takenawa Tadaomi , Nakauchi Hiromitsu 
Published: July 2007

Abstract
Actin polymerization is crucial in throm-bopoiesis, platelet adhesion, and mega-karyocyte (MK) and platelet spreading. The Wiskott-Aldrich syndrome protein (WASp) homolog WAVE functions downstream of Rac and plays a pivotal role in lamellipodia formation. While MKs and platelets principally express WAVE1 and WAVE2, which are associated with Abi1, the physiologic significance of WAVE isoforms remains undefined. We generated WAVE2−/− embryonic stem (ES) cells because WAVE2-null mice die by embryonic day (E) 12.5. We found that while WAVE2−/− ES cells differentiated into immature MKs on OP9 stroma, they were severely impaired in terminal differentiation and in platelet production. WAVE2−/− MKs exhibited a defect in peripheral lamellipodia on fibrinogen even with phorbol 12-myristate 13-acetate (PMA) costimulation, indicating a requirement of WAVE2 for integrin αIIbβ3-mediated full spreading. MKs in which expression of Abi1 was reduced by small interfering RNA (siRNA) exhibited striking similarity to WAVE2−/− MKs in maturation and spreading. Interestingly, the knockdown of IRSp53, a Rac effector that preferentially binds to WAVE2, impaired the development of lamellipodia without affecting proplatelet production. In contrast, thrombopoiesis in vivo and platelet spreading on fibrinogen in vitro were intact in WAVE1-null mice. These observations clarify indispensable roles for the WAVE2/Abi1 complex in αIIbβ3-mediated lamellipodia by MKs and platelets through Rac and IRSp53, and additionally in thrombopoiesis independent of Rac and IRSp53.
PPARγ regulates the function of human dendritic cells primarily by altering lipid metabolism
Authors: Szatmari Istvan , Töröcsik Daniel , Agostini Maura , Nagy Tibor , Gurnell Mark , Barta Endre , Chatterjee Krishna , Nagy Laszlo 
Published: July 2007

Abstract
Activation of the lipid-regulated nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) modifies the immunophenotype of monocyte-derived dendritic cells (DCs). However it has not been analyzed in a systematic manner how lipid metabolism and immune regulation are connected at the transcriptional level via this receptor. Here we present the genome-wide expression analyses of PPARγ-instructed human DCs. Receptor activation was achieved by exogenous, synthetic as well as endogenous, natural means. More than 1000 transcripts are regulated during DC development by activation of PPARγ; half of the changes are positive effects. These changes appear to enhance and modulate the robust gene expression alterations associated with monocyte to DC transition. Strikingly, only genes related to lipid metabolism are overrepresented among early induced genes. As a net consequence, lipid accumulation appears to be diminished in these cells. In contrast, genes related to immune response are regulated after 24 hours, implying the existence of indirect mechanisms of modulation. Receptor dependence was established by using DCs of patients harboring a dominant-negative mutation of PPARγ. Our data show that PPARγ acts as a mostly positive transcriptional regulator in human developing DCs, acting primarily through controlling genes involved in lipid metabolism and via this, indirectly modifying the immune phenotype.
Premature ventricular complex-induced chronic cough and cough syncope
Authors: Stec S. , Da̧browska M. , Zaborska B. , Bielicki P. , Maskey-Warzęchowska M. , Tarnowski W. , Chazan R. , Kulakowski P. 
Published: July 2007

The present case study reports a case of chronic cough and cough syncope associated with frequent premature ventricular complexes (PVCs).Careful analysis of cough-related symptoms and ECG monitoring led to the suspicion of PVC-induced cough. A coincidence between PVCs and episodes of cough was also documented by a portable multichannel recorder. Moreover, Doppler echocardiography revealed a PVC-induced transient increase in the pulmonary artery blood flow.After exclusion of other possible aetiologies, complete relief of chronic cough and cough syncope was achieved by radiofrequency ablation of the arrhythmogenic focus located in the right ventricular outflow tract.Premature ventricular complexes should be considered as a cause of chronic cough and cough syncope and an interdisciplinary cooperation can lead to successful diagnosis and treatment of this condition.
The effects of hypoxia on the cells of the pulmonary vasculature
Authors: Pak O. , Aldashev A. , Welsh D. , Peacock A. 
Published: July 2007

Pulmonary hypertension is associated with remodelling of pulmonary vessels. Chronic hypoxia is a common cause of pulmonary hypertension and pulmonary vascular remodelling. Vascular remodelling is characterised largely by fibroblast, smooth muscle and endothelial cell proliferation, which results in lumen obliteration. Chronic hypoxia elicits expression of mitogens, growth factors and cytokines by fibroblasts and endothelial cells, and also the suppression of endothelial nitric oxide synthase. Although hypoxic pulmonary vascular remodelling is associated with medial hypertrophy, manyin vitrostudies have found that hypoxia does not lead to a direct increase in smooth muscle cell proliferation. This paradox is not well understood and this review aims to examine the various reasons why this might be so. The present authors reviewed data fromin vitrostudies and also considered whether hypoxia could act on adjacent cells such as fibroblasts and endothelial cells to trigger smooth muscle cell proliferation. It is possible that hypoxia is sensed by fibroblasts, endothelial cells, or both, and relayed to adjacent pulmonary artery smooth muscle cells by intercellular signalling, causing proliferation.The present article reviews the data fromin vitrostudies of hypoxia on the three cellular components of the pulmonary vascular wall, namely endothelial cells, smooth muscle cells and fibroblasts.
The pattern recognition receptor Nod1 activates CCAAT/enhancer binding protein β signalling in lung epithelial cells
Authors: Barton J. L. , Berg T. , Didon L. , Nord M. 
Published: July 2007

The innate immune receptor nucleotide-binding oligomerisation domain protein 1 (Nod1) recognises peptidoglycan containingmeso-diaminopimelic acid found in all Gram-negative and some Gram-positive bacteria. Nod1 has been shown to activate nuclear factor (NF)-κB. The aim of the present study was to examine the expression of Nod1 in the lung, particularly in lung epithelial cells, and to investigate the activation of CCAAT/enhancer binding protein (C/EBP) transcription factors downstream of the Nod1 receptor in these cells.The expression of Nod1 in mouse lung was examined using immunohistochemistry. A tissue array was used to determine the expression pattern in the human lung. Signalling downstream of Nod1 was examined in the human lung epithelial cell type, BEAS-2B, by electrophoretic mobility shift assay and reporter gene activation.Nod1 expression was seen in various cell types in the lung, including epithelial cells. Activation of Nod1 in these cells resulted in modest activation of NF-κB, together with strong activation of the C/EBP transcription factors, particularly C/EBPβ. This activation appears to be independent ofde novoprotein synthesis.The present study showed that nucleotide-binding oligomerisation domain protein 1 is expressed in lung epithelial cells. The results demonstrate a novel pathway downstream of the nucleotide-binding oligomerisation domain protein 1 receptor in these cells and suggest that C/EBPβ may play a role in immune responses tomeso-diaminopimelic acid-containing bacteria in the lung.
Trends in ethical and legal frameworks for the use of human biobanks
Authors: Cambon-Thomsen A. , Rial-Sebbag E. , Knoppers B. M. 
Published: July 2007

Numerous studies of genetic epidemiology and post-genomics in respiratory diseases rely on the use of biobanks, defined as organised biological sample collections with associated personal and clinical data. The use of biobanks is increasing and raises several ethical issues. What are the ethical trends and legal frameworks in the post-genomic era? Are there new issues in relation to the developments of techniques and new study designs? How does this affect the clinician’s attitudes and relationship with the patients?The main ethical issues encountered are: informed consent; confidentiality; secondary use of samples and data over time; return of results; and data sharing. Different levels and modalities of dealing with such issues are identified and vary from legally binding measures to “soft” regulations, such as ethical recommendations by various committees or professional organisations.A further level of complexity appears with the increasing international dimension of such activities in a context in which national positions vary on those topics. There is a tension between a necessary level of diversity in ethical positions and an indispensable common pedestal of principles and procedures to manage these issues in order to foster research.Current legal and ethical trends favour the facilitation of secondary use of samples, more biobank openness, balanced with a growing attention to dialogue and public/stakeholder consultation, an increased role for research ethics committees and more sophisticated data protection and governance structures.
Evolution of outcome measures in schizophrenia
Authors: Burns Tom 
Published: July 2007

SummaryOutcome has been a key concern in schizophrenia since Kraepelin first identified the disorder. The outcomes that researchers and clinicians use and value in their work with it have changed to reflect evolving theories about it and the available interventions. This supplement tracks those changes and examines the merits and use of structured approaches to understand this most complex disorder
Social outcomes in schizophrenia
Authors: Priebe Stefan 
Published: July 2007

BackgroundOutcomes reflecting the social situation are widely considered as important in the treatment of people with schizophreniaAimsTo review concepts of social outcomes in schizophrenia and the corresponding assessment instrumentsMethodNon-systematic literature review and reflection on conceptual and methodological issuesResultsConcepts of social outcomes in schizophrenia lack agreed definitions and theoretical models. A fundamental issue is the distinction between objective and subjective indicators. More research has focused on subjective indicators, which are only weaklly correllated with objective life situation and show consistent correlations with mood. Various assessment instruments have been developed pragmatically, particularly to measure quality of life and social functioning, and the literature provides extensive data for comparisonConclusionsEstablished instruments exist to measure social outcomes in schizophrenia. Their use requires an awareness of the specific strengths and limitations
Outcomes of public concern in schizophrenia
Authors: Kooyman Iain , Dean Kimberlie , Harvey Samuel , Walsh Elizabeth 
Published: July 2007

BackgroundSchizophrenia is known to be associated with a range of adverse outcomes, which have an impact at the societal level and are therefore of public concernAimsTo examine the epidemiology and methods for measuring six adverse outcomes in schizophrenia: violence, victimisation, suicide/self-harm, substance use, homelessness and unemploymentMethodAreview of the literature was carried out for each adverse outcome, with attention to critical appraisal of existing measurement toolsResultsSchizophrenia is associated strongly with all six outcomes, although research has mainly focused on violence. Each outcome acts as a risk factor for at least some of the other outcomes. There are few standardised or validated measures for these'hard' outcomes. Each measure has inherent biases but a growing trend is for these to be minimised by using multiple measuresConclusionsAsingle instrument which systematically measures multiple societal outcomes of schizophrenia would be extremely useful for both clinical and research purposes
Cognition as an outcome measure in schizophrenia
Authors: Kraus Michael S. , Keefe Richard S. E. 
Published: July 2007

BackgroundCognitive deficits are a core feature of schizophrenia. These deficits are not caused by medication or symptoms, and have a dramatic negative effecton real-world functioningAimsTo critically examine a selection of the most common batteries used to assess cognition in schizophreniaMethodLiterature review of cognitive assessment batteries for use in schizophreniaResultsA wide variety of neuro-cognitive test batteries have been developed or adapted to assess cognition in schizophrenia. These differ in time requirements, repeatability, ease of administration, degree of face validity, availability of co-normative data and degree to which results can be parsed into separate domains of cognitive functioning. The most appropriate depends on the setting and the question being addressedConclusionsCognitive outcome measures have reshaped our understanding of schizophrenia and will be essential tools for unravelling the aetiology of the disease and designing more effective interventions
Neuroimaging and other neurobiological indices in schizophrenia: relationship to measurement of functional outcome
Authors: Waddington John L. 
Published: July 2007

BackgroundAs understanding of the pathobiology of schizophrenia increases, the challenge is to relate such measures to outcome at a functional levelAimsTo consider our current understanding of how neurobiological variables relate to functional outcome and might constitute outcome measures in their own rightMethodCritical appraisal of recent evidence on structural and functional imaging, neurological evaluation, early neurodevelopmental indices, genomics, proteomics, metabolomics and apoptotic mechanisms in relation to outcomeResultsStudies conducted prospectively from the first episode of schizophrenia are generating more reliable findings but currently lack predictive power. Prediction of transition from ‘high-risk’ status to first episode has proved somewhat more fruitful, but the gain has been modest and circumscribedConclusionsOur current level of understanding does not yet allow the generation of predictive models on an individual patient basis. Genomic and metabolomic studies hold particular potential for generating clinically meaningful ‘biomarkers’ but considerable further work is necessary
Schizophrenia outcome measures in the wider international community
Authors: Isaac Mohan , Chand Prabhat , Murthy Pratima 
Published: July 2007

BackgroundOutcome of schizophrenia has been described as favourable in low-and middle-income countries. Recently, researchers have questioned these findingsAimsTo examine the outcome studies carried out in different countries specifically looking atthose from low-and middle-income countriesMethodsLong-term course and outcome studies in schizophrenia were reviewedResultsA wide variety of outcome measures are used. The most frequent are clinical symptoms, hospitalisation and mortality (direct indicators), and social/ occupational functioning, marriage, social support and burden of care (indirect indicators). Areas such as cognitive function, duration of untreated psychosis, quality of life and effect of medication have not been widely studied in low-and middle-income countriesConclusionsThe outcome of schizophrenia appears to be better in low-and middle-income countries. A host of sociocultural factors have been cited as contributing to this but future research should aim to understand this better outcome. There is a need for more culture-specific instruments to measure outcomes
Characteristics and activities of acute psychiatric in-patient facilities: national survey in Italy
Authors: De Girolamo Giovanni , Barbato Angelo , Bracco Renata , Gaddini Andrea , Miglio Rossella , Morosini Pierluigi , Norcio Bruno , Picardi Angelo , Picardi Angelo , Rossi Elisabetta , Rucci Paola , Santone Giovanni , Dell'Acqua Giuseppe 
Published: July 2007

BackgroundLegislation in 1978 led to the gradual replacement of mental hospitals in Italy with a full range of community-based services, including facilities for acute in-patient care.AimsTo survey the main characteristics of Italian public and private in-patient facilities for acute psychiatric disorders.MethodStructured interviews were conducted with each facility's head psychiatrist in all Italian regions, with the exception of Sicily.ResultsOverall, Italy (except Sicily) has atotal of 4108 public in-patient beds in 319 facilities, with 0.78 beds for every 10 000 inhabitants, and 4862 beds in 54 private in-patient facilities, with 0.94 beds per 10 000 inhabitants. In 2001 the rates of psychiatric admissions and admitted patients per 10 000 inhabitants were 26.7 and 17.8 respectively. In the same year the percentage of involuntary admissions was 12.9%, for atotal of 114 570 hospital days. Many in-patient facilities showed significant limitations in terms of architectural and logistic characteristics. Staffing showed a great variability among facilities.ConclusionsThe overall number of acute beds per 10 000 inhabitants is one of the lowest in Europe. The survey has provided evidence of two parallel systems of in-patient care, a public one and a private one, which are not fully interchangeable.
Social identification and post-traumatic stress symptoms in post-conflict Northern Ireland
Authors: Muldoon Orla T. , Downes Ciara 
Published: July 2007

BackgroundUnderstanding of the psychological impact of politically motivated violence is poor.AimsTo examine the prevalence of post-traumatic symptoms subsequent to the ‘troubles' in Northern Ireland.MethodA telephone survey of 3000 adults, representative of the population in Northern Ireland and the border counties of the Irish Republic, examined exposure to political violence, post-traumatic stress disorder (PTSD) and national identity.ResultsTen per cent of respondents had symptoms suggestive of clinical PTSD. These people were most likely to come from low-income groups, rate national identity as relatively unimportant and have higher overall experience of the ‘troubles' than other respondents.ConclusionsDirect experience of violence and poverty increase the risk of PTSD, whereas strong national identification appears to reduce this risk.
Frontal release signs and cognition in people with schizophrenia, their siblings and healthy controls
Authors: Hyde Thomas M. , Goldberg Terry E. , Egan Michael F. , Lener Marc C. , Weinberger Daniel R. 
Published: July 2007

BackgroundFrontal release signs, a subset of neurological soft signs, are common in schizophrenia.AimsTo explore the relationship between frontal release signs and neuropsychological tests of frontal lobe function in people with schizophrenia, their siblings and healthy controls.MethodNeuropsychological tests and frontal release signs were measured in a cohort of index cases (n=302), their siblings (n=240) and healthy controls (n=346).ResultsThe mean total score of frontal release signs was 1.5 (s.d. = 1.58) in the schizophrenia group, 0.54 (s.d.=0.92) for siblings and 0.42 (s.d.=0.77) for controls. Schizophrenia group scores were greater than healthy control or sibling cohort scores (P< 0.0001), which did not differ. In all three cohorts, right grasp reflex scores positively correlated with number of perseverative errors on the Wisconsin Card Sort Task (P<0.05). In the schizophrenia group, frontal release signs scores showed an inverse correlation with IQ (R= −0.199,P<0.0005).ConclusionsOur findings of relationships between frontal release signs and cognitive assays of cortical dysfunction and the increased frequency of these signs in people with schizophrenia implicate a cortical origin for these clinical signs and evidence of frontal lobe dysfunction in this disorder.
Emotion recognition and genetic vulnerability to schizophrenia
Authors: Bediou Benoit , Asri Fatima , Brunelin Jerome , Krolak-Salmon Pierre , D'Amato Thierry , Saoud Mohamed , Tazi Imane 
Published: July 2007

BackgroundEpidemiological studies of schizophrenia suggest that this disorder has a substantial genetic component. Cognitive and social abilities, as well as the volumes of brain regions involved in emotion processing, have been found to be distributed along a continuum when comparing patients, siblings and controls, with siblings showing intermediate scores.AimsTo establish whether facial expression recognition is impaired in unaffected siblings of patients.MethodEmotion and gender recognition were evaluated in a three-group pre–post study design in drugnaive patients with first-episode schizophrenia (n=40) and their unaffected siblings (n=30) compared with controls (n=26).ResultsPatients and their healthy siblings showed impaired emotion recognition but normal gender recognition compared with controls. Patients' performance did not improve despite effective clinical stabilisation.ConclusionsImpaired performance in healthy siblings and time stability in patients provides evidence of impairment of facial emotion recognition as an actual phenotype of schizophrenia.
Treatment of depression in primary care
Authors: Weich Scott , Nazareth Irwin , Morgan Louise , King Michael 
Published: July 2007

BackgroundDepression is prevalent, costly and often undertreated.AimsTo test the hypothesis that people with low socio-economic status are least likely to receive and adhere to evidence-based treatments for depression, after controlling for clinical need.MethodIndividuals with an ICD-10 depressive episode in the past 12 months (n = 866) were recruited from 7271 attendees in 36 general practices in England and Wales. Depressive episodes were identified using the 12-month Composite International Diagnostic Interview. Treatment receipt and adherence were assessed by structured interview, and rated using evidence-based criteria.ResultsWe identified 332 individuals (38.3%) who received and adhered to evidence-based treatment. There were few socio-economic differences in treatment allocation. Although those without educational qualifications were least likely to receive psychological treatments (OR = 0.55, 95% CI 0.34–0.89, P = 0.02), this association was not statistically significant after adjusting for depression severity.ConclusionsWe found no evidence of inverse care in the treatment of moderate and severe depression in primary care in England and Wales.
Deployment-related stress and trauma in Dutch soldiers returning from Iraq
Authors: Engelhard Iris M. , Van Den Hout Marcel A. , Weerts Jos , Arntz Arnoud , Hox Joop J. C. M. , McNally Richard J. 
Published: July 2007

BackgroundSome questionnaire studies have shown increased mental health problems, including probable posttraumatic stress disorder (PTSD), in soldiers deployed to Iraq.AimsTo test prospectively whether such problems change over time and whether questionnaires provide accurate estimates of deployment-related PTSD compared with a clinical interview.MethodsDutch infantry troops from three cohorts completed questionnaires before deployment to Iraq (n=479), and about 5 months (n=382, 80%) and 15 months (n=331, 69%) thereafter. Post-traumatic stress disorder was evaluated by questionnaire and clinical interview.ResultsThere were no group changes for general distress symptoms. The rates of PTSD for each cohort were 21, 4 and 6% based on questionnaires at 5 months. The deployment-related rates of PTSD based on the clinical interview were 4, 3 and 3%.ConclusionsThere was a specific effect of deployment on mental health for a small minority. Questionnaires eliciting stress symptoms gave substantial overestimations of the rate of PTSD.