bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transforming growth factor-β1 down-regulates expression of chemokine stromal cell–derived factor-1: functional consequences in cell migration and adhesion
Authors: Wright Natalia , de Lera Teresa Laín , García-Moruja Carelia , Lillo Rosa , García-Sánchez Félix , Caruz Antonio , Teixidó Joaquin 
Published: June 2003

AbstractChemokine stromal cell–derived factor-1 (SDF-1) is expressed by bone marrow (BM) stromal cells and plays key roles in BM cell migration. Modulation of its expression could affect the migratory capacity of cells trafficking the BM, such as hematopoietic progenitor and leukemic cells. Transforming growth factor-β1 (TGF-β1) is present in the BM environment and constitutes a pivotal molecule controlling BM cell proliferation and differentiation. We used the BM stromal cell line MS-5 as a model to investigate whether SDF-1 expression constitutes a target for TGF-β1 regulation and its functional consequences. We show here that TGF-β1 down-regulates SDF-1 expression, both at the mRNA level, involving a decrease in transcriptional efficiency, and at the protein level, as detected in lysates and supernatants from MS-5 cells. Reduction of SDF-1 in supernatants from TGF-β1–treated MS-5 cells correlated with decreased, SDF-1–dependent, chemotactic, and transendothelial migratory responses of the BM model cell lines NCI-H929 and Mo7e compared with their responses to supernatants from untreated MS-5 cells. In addition, supernatants from TGF-β1–exposed MS-5 cells had substantially lower efficiency in promoting integrin α4β1–mediated adhesion of NCI-H929 and Mo7e cells to soluble vascular cell adhesion molecule-1 (sVCAM-1) and CS-1/fibronectin than their untreated counterparts. Moreover, human cord blood CD34+ hematopoietic progenitor cells displayed SDF-1–dependent reduced responses in chemotaxis, transendothelial migration, and up-regulation of adhesion to sVCAM-1 when supernatants from TGF-β1–treated MS-5 cells were used compared with supernatants from untreated cells. These data indicate that TGF-β1–controlled reduction in SDF-1 expression influences BM cell migration and adhesion, which could affect the motility of cells trafficking the bone marrow.
Intronic BCL-6 mutations are preferentially targeted to the translocated allele in t(3;14)(q27;q32) non-Hodgkin B-cell lymphoma
Authors: Jardin Fabrice , Bastard Christian , Contentin Nathalie , Parmentier Françoise , Picquenot Jean-Michel , Tilly Hervé , Stevenson Freda K. , Sahota Surinder S. 
Published: June 2003

AbstractTranslocations and somatic mutations are common genetic alterations of the BCL-6 gene on chromosome 3q27 in B-cell lymphoma, with implications for lymphomagenesis. The 2 events may have linked origins and can influence juxtaposed loci. To evaluate this further, we compared mutations occurring within the major mutation cluster region of the translocated and untranslocated BCL-6 alleles in 7 t(3;14)(q27;14q32) lymphomas. In 6 of 7 cases, the translocated allele revealed significantly higher mutations (mean, 5.8 × 10–2 bp–1) than did the untranslocated allele (mean, 5.3 × 10–3 bp–1; P &lt; .01). The increase mapped to der(14q32), which retains the BCL-6 promoter and is transcriptionally active, as revealed by fusion transcripts and ongoing somatic mutations, absent in the der(3q27) region. These results indicate that enhanced mutational activity at the translocated allele may be a consequence of loss of cis regulatory elements or gain of IgH enhancer elements. Junctional sequences indicate translocation origins from earlier BCL-6 mutations and switch recombinase events.
Efficacy of imatinib mesylate in the treatment of idiopathic hypereosinophilic syndrome
Authors: Cortes Jorge , Ault Patricia , Koller Charles , Thomas Deborah , Ferrajoli Alessandra , Wierda William , Rios Mary B. , Letvak Laurie , Kaled Elizabeth S. , Kantarjian Hagop 
Published: June 2003

Abstract
Idiopathic hypereosinophilic syndrome (HES) is a myeloproliferative disorder characterized by persistent eosinophilia and organ involvement. Different treatments have been investigated in HES with modest success. It has been suggested that imatinib is active in HES. We treated 9 patients with HES with 100 mg imatinib daily. Doses for patients without response after 4 weeks were increased to 400 mg daily. Prior therapy had failed for 7 patients. Five patients responded: 4 achieved sustained complete remission lasting a median of 12+ weeks (range, 9+ to 36+ weeks), and 1 had a transient response. One patient died in complete remission. Responses occurred within 4 weeks of therapy; only 1 responder required an increase in dose to 400 mg daily. Three of 4 nonresponders failed to respond to an increase in dose. Toxicity was minimal. We conclude that imatinib therapy is effective for HES.
MHC class II signal transduction in human dendritic cells induced by a natural ligand, the LAG-3 protein (CD223)
Authors: Andreae Susanne , Buisson Sandrine , Triebel Frédéric 
Published: June 2003

AbstractOn encountering a danger signal, dendritic cells (DCs) undergo a complex maturation process and become specialized in antigen presentation. We previously reported that engagement of major histocompatibility complex (MHC) class II molecules located on immature DCs in membrane rafts by lymphocyte activation gene-3 (LAG-3; CD223) leads to DC maturation. In contrast, exposure of DCs to class II–specific monoclonal antibodies (mAbs) did not lead to maturation. Here, we have investigated the signal transduction pathways involved in the LAG-3–induced maturation of human monocyte-derived DCs. We first show that areas of raft aggregation (both cholesterol rich and CDw78 microdomains) could be visualized using a soluble LAG-3 protein and confocal microscopy. Engagement of class II molecules by both its natural ligand LAG-3 and class II mAb induces rapid protein phosphorylation of phospholipase Cγ2 (PLCγ2) and p72syk as well as activation of phosphatidyl inositol 3-kinase/Akt, p42/44 extracellular signal-regulated protein kinase, and p38 mitogen-activated protein kinase pathways. Studies using inhibitors demonstrate that these 3 pathways are all important in inducing the maturation process of LAG-3–stimulated DCs. When class II molecules were ligated with LAG-3 versus specific antibody, differences in the phosphorylation pattern of c-Akt were observed. Thus, MHC class II signaling in DCs involves several pathways that have to be finely regulated to lead to cell activation and maturation.
Anergic T cells exert antigen-independent inhibition of cell-cell interactions via chemokine metabolism
Authors: James Martha J. , Belaramani Lavina , Prodromidou Kanella , Datta Arpita , Nourshargh Sussan , Lombardi Giovanna , Dyson Julian , Scott Diane , Simpson Elizabeth , Cardozo Lorraine , Warrens Anthony , Szydlo Richard M. , Lechler Robert I. , Marelli-Berg Federica M. 
Published: June 2003

AbstractDue to their ability to inhibit antigen-induced T-cell activation in vitro and in vivo, anergic T cells can be considered part of the spectrum of immunoregulatory T lymphocytes. Here we report that both murine and human anergic T cells can impair the ability of parenchymal cells (including endothelial and epithelial cells) to establish cell-cell interactions necessary to sustain leukocyte migration in vitro and tissue infiltration in vivo. The inhibition is reversible and cell-contact dependent but does not require cognate recognition of the parenchymal cells to occur. Instrumental to this effect is the increased cell surface expression and enzymatic activity of molecules such as CD26 (dipeptidyl-peptidase IV), which may act by metabolizing chemoattractants bound to the endothelial/epithelial cell surface. These results describe a previously unknown antigen-independent anti-inflammatory activity by locally generated anergic T cells and define a novel mechanism for the long-known immunoregulatory properties of these cells.
Anti–third-party veto CTLs overcome rejection of hematopoietic allografts: synergism with rapamycin and BM cell dose
Authors: Bachar-Lustig Esther , Reich-Zeliger Shlomit , Reisner Yair 
Published: June 2003

AbstractSeveral bone marrow cells and lymphocyte subpopulations, known as “veto cells,” were shown to induce transplantation tolerance across major histocompatibility antigens. Some of the most potent veto cells are of T-cell origin, and in particular a very strong veto activity was documented for cytotoxic T-lymphocyte (CTL) lines or clones. However, these cells also possess marked graft-versus-host (GVH) reactivity. In the present study we evaluated a new approach to deplete CTLs of antihost clones by stimulating the donor T cells against third-party stimulators in the absence of exogenous interleukin 2 (IL-2). We demonstrate that such CTLs are depleted of GVH reactivity while maintaining marked veto activity in vitro. Furthermore, marked synergism was exhibited between the veto CTLs and rapamycin when tested in a murine model, which measures T-cell–mediated bone marrow allograft rejection, or in sublethally irradiated allogeneic hosts.Our results suggest that engraftment of early progenitors could be enhanced by using host-nonreactive anti–third-party CTLs, in conjunction with nonmyeloablative rapamycin-based conditioning protocols, thereby significantly reducing the toxicity of allogeneic transplantation.
Induction of allopeptide-specific human CD4+CD25+ regulatory T cells ex vivo
Authors: Jiang Shuiping , Camara Niels , Lombardi Giovanna , Lechler Robert I. 
Published: June 2003

AbstractAlthough CD4+CD25+ regulatory T cells are pivotal in the prevention of autoimmunity and appear to mediate transplantation tolerance, little is known concerning their antigen specificity. Here we describe the induction of a human CD4+CD25+ regulatory T-cell line specific for a defined peptide alloantigen (human leukocyte antigen A2 [HLA-A2] 138-170) by priming purified CD4+CD25+ cells ex vivo. The regulatory cells were anergic and retained their ability to suppress antigen-driven responses of CD4+CD25– cells. They inhibited not only interleukin 2 (IL-2) secretion by CD4+CD25– T cells specific for the same peptide but also direct alloresponse of naive CD4+CD25– T cells stimulated by semiallogeneic dendritic cells (DCs) in the presence of the peptide (“linked suppression”). They also suppressed the response of CD4+ T cells specific for viral and bacterial antigens. The suppressive T-cell line showed sustained high CD25 expression. These findings suggest that peripheral CD4+CD25+ regulatory cells are a precommitted cell lineage from which cells with specificity for non–self-peptides can be selected. This may pave the way for inducing and expanding peptide antigen-specific regulatory T cells ex vivo for cell therapy in transplantation, allergy, and autoimmune disease.
Acid–base status of critically ill patients with acute renal failure: analysis based on Stewart–Figge methodology
Authors: Rocktaeschel Jens , Morimatsu Hiroshi , Uchino Shigehiko , Goldsmith Donna , Poustie Stephanie , Story David , Gutteridge Geoffrey , Bellomo Rinaldo 
Published: June 2003

Abstract
Introduction
The aim of the present study is to understand the nature of acid–base disorders in critically ill patients with acute renal failure (ARF) using the biophysical principles described by Stewart and Figge. A retrospective controlled study was carried out in the intensive care unit of a tertiary hospital.

Materials and methods
Forty patients with ARF, 40 patients matched for Acute Physiology and Chronic Health Evaluation II score (matched control group), and 60 consecutive critically ill patients without ARF (intensive care unit control group) participated. The study involved the retrieval of biochemical data from computerized records, quantitative biophysical analysis using the Stewart–Figge methodology, and statistical comparison between the three groups. We measured serum sodium, potassium, magnesium, chloride, bicarbonate, phosphate, ionized calcium, albumin, lactate and arterial blood gases.

Results
Intensive care unit patients with ARF had a mild acidemia (mean pH 7.30 ± 0.13) secondary to metabolic acidosis with a mean base excess of -7.5 ± 7.2 mEq/l. However, one-half of these patients had a normal anion gap. Quantitative acid–base assessment (Stewart–Figge methodology) revealed unique multiple metabolic acid–base processes compared with controls, which contributed to the overall acidosis. The processes included the acidifying effect of high levels of unmeasured anions (13.4 ± 5.5 mEq/l) and hyperphosphatemia (2.08 ± 0.92 mEq/l), and the alkalinizing effect of hypoalbuminemia (22.6 ± 6.3 g/l).

Conclusions
The typical acid–base picture of ARF of critical illness is metabolic acidosis. This acidosis is the result of the balance between the acidifying effect of increased unmeasured anions and hyperphosphatemia and the lesser alkalinizing effect of hypoalbuminemia.
Older community residents with depression: long-term treatment with sertraline
Authors: Wilson K. C. M. , Mottram P. G. , Ashworth L. , Abou-Saleh M. T. 
Published: June 2003

BackgroundDespite a growing use of selective serotonin reuptake inhibitors in older people, only one trial has examined their prophylactic efficacy in people aged 65 years and over.AimsTo examine the efficacy of sertraline in preventing the recurrence of depression in older people living in the community.MethodParticipants were openly treated with sertraline and then randomised into a double-blind, placebo-controlled continuation/maintenance study of about 2 years duration. Drug dosage was maintained at levels that achieved remission.ResultsNo significant difference between the sertraline and placebo groups was found in the proportion of recurrences (–7.9%; 95% CI –28.06 to 12.23). Increased age and minor residual symptoms during the continuation phase were associated with recurrence.ConclusionsSertraline at therapeutic dosage does not provide significant protection against recurrence.
Modelling the impact of clozapine on suicide in patients with treatment-resistant schizophrenia in the UK
Authors: Duggan Andy , Warner Juliet , Knapp Martin , Kerwin Robert 
Published: June 2003

BackgroundSchizophrenia is a major cause of suicide, and symptoms characteristic of treatment-resistant disease are strong risk factors. Clozapine reduces symptoms in 60% of such patients and significantly decreases the risk of suicide.AimsTo model the impact of increased clozapine prescribing on lives saved and resource utilisation.MethodA model was built to compare current levels of clozapine prescribing with a scenario in which all suitable patients with treatment-resistant schizophrenia received clozapine.ResultsIt was estimated that an average of 53 lives could be saved in the UK each year. If clozapine is cost-neutral, the cost per life-year saved is $.5108. If clozapine achieves a 10% reduction in annual support costs, the net saving is $8.7 million per annum. An average of 167 acute beds would be freed each year.ConclusionsThe use of clozapine in treatment-resistant schizophrenia saves lives, frees resources and is cost-effective.
Morphology of the anterior cingulate cortex in young men at ultra-high risk of developing a psychotic illness
Authors: Yücel Murat , Wood Stephen J. , Phillips Lisa J. , Stuart Geoffrey W. , Smith Deidre J. , Yung Alison , Velakoulis Dennis , Mcgorry Patrick D. , Pantelis Christos 
Published: June 2003

BackgroundThe anterior cingulate cortex (ACC) is consistently implicated in the pathophysiology of schizophrenia, and our own work has identified morphological anomalies in the ACC of people with this disorder.AimsTo examine whether ACC morphological anomalies are present in a group at ultra-high risk of psychosis and whether such anomalies can be used to predict the subsequent development of a psychotic illness.MethodMagnetic resonance imaging of 75 healthy volunteers and 63 people at ultra-high risk of developing a psychotic disorder (all right-handed males) was used to examine ACC sulcal and gyral features.ResultsCompared with the controls, significantly fewer people in the ultra-high risk group had a well-developed left paracingulate sulcus and significantly more had an interrupted left cingulate sulcus. There was no difference between those who did (n=21) and did not (n=42) subsequently develop a psychotic illness.ConclusionsAlthough ACC anomalies are present in young people considered to be at ultra-high risk of psychosis, they do not identify individuals who subsequently make the transition to psychosis.
Engagement of brain areas implicated in processing inner speech in people with auditory hallucinations
Authors: Shergill Sukhwinder S. , Brammer Michael J. , Fukuda Rimmei , Williams Steven C. R. , Murray Robin M. , McGuire Philip K. 
Published: June 2003

BackgroundThe neurocognitive basis of auditory hallucinations is unclear, but there is increasing evidence implicating abnormalities in processing inner speech. Previous studies have shown that people with schizophrenia who were prone to auditory hallucinations demonstrated attenuated activation of brain areas during the monitoring of inner speech.AimsTo investigate whether the same pattern of functional abnormalities would be evident as the rate of inner speech production was varied.MethodEight people with schizophrenia who had a history of prominent auditory hallucinations and eight control participants were studied using functional magnetic resonance imaging while the rate of inner speech generation was varied experimentally.ResultsWhen the rate of inner speech generation was increased, the participants with schizophrenia showed a relatively attenuated response in the right temporal, parietal, parahippocampal and cerebellar cortex.ConclusionsIn people with schizophrenia who are prone to auditory hallucinations, increasing the demands on the processing of inner speech is associated with attenuated engagement of the brain areas implicated in verbal self-monitoring.
Suicide following deliberate self-harm: long-term follow-up of patients who presented to a general hospital
Authors: Hawton Keith , Zahl Daniel , Weatherall Rosamund 
Published: June 2003

BackgroundDeliberate self-harm (DSH) is the strongest risk factor for future suicide. Up-to-date information on the extent of risk is lacking.AimsTo investigate the risk of suicide after DSH during a long follow-up period.MethodA mortality follow-up study to 2000 was conducted on 11583 patients who presented to hospital after DSH between 1978 and 1997. Data were obtained from a general hospital DSH register in Oxford and the Office for National Statistics, and from equivalent mortality registers in Scotland and Northern Ireland.ResultsThree hundred patients had died by suicide or probable suicide. The risk in the first year of follow-up was 0.7% (95% CI 0.6–0.9%), which was 66 (95% CI 52–82) times the annual risk of suicide in the general population. The risk after 5 years was 1.7%, at 10 years 2.4% and at 15 years 3.0%. The risk was far higher in men than in women (hazard ratio 2.8, 95% CI 2.2–3.6). In both genders it increased markedly with age at initial presentation.ConclusionsFollowing DSH there is a significant and persistent risk of suicide, which varies markedly between genders and age groups. Reduction in the risk of suicide following DSH must be a key element in national suicide prevention strategies.
Prescribing errors in psychiatry
Authors: Paton Carol , Gill-Banham Stuart 
Published: June 2003

Aims and MethodThe Department of Health would like to see serious prescribing errors reduced by 40% by 2005. Little is currently known about prescribing errors made by psychiatrists. The aim of this study was to describe prescribing errors within psychiatry by analysing interventions made by pharmacists. Members of the SouthEast Thames Psychiatric Pharmacists' Network were asked to record details of prescribing errors made in their trusts during the month of May 2002.ResultsFive hundred and seventy-nine errors were reported during the study period. The majority of errors were due to clerical oversights or failure to apply clinical knowledge. In 63 cases (11%), the error could have resulted in a serious outcome.Clinical ImplicationsPrescribing errors are a daily occurrence in Mental HealthTrusts, and a potentially serious error is likely to occur on a weekly basis in an average trust. Steps need to be taken to minimise the chances of errors occurring.
Drug and alcohol misuse among in-patients with psychotic illnesses in three inner-London psychiatric units
Authors: Phillips Prashant , Johnson Sonia 
Published: June 2003

Aims and MethodWard staff were asked to rate whether in-patients with a diagnosis of functional psychotic illness also met criteria for a diagnosis of alcohol or drug misuse or dependence during the preceding 6 months. Those who demonstrated such evidence were then asked to report the nature and extent of their substance use and whether they continued to use as in-patients.Results264 in-patients with psychotic illness were screened for evidence of recent or current alcohol or drug misuse. According to staff reports, 127 (48.9%) met the criteria for substance misuse or dependence. The mean age of those with ‘dual diagnosis' was 34.7 years and 72% were male. Eighty-three (83%) of those with a history of current or recent alcohol or drug misuse reported that they had continued to use alcohol and/or illicit drugs in the in-patient wards during their current admission.Clinical ImplicationsIt appears difficult to prevent in-patients with drug or alcohol misuse problems from continuing to use substances in hospital. Further consideration and investigation of how best to manage this group is therefore required.
Leptin Signaling in the Hypothalamus during Chronic Central Leptin Infusion
Authors: Pal Rekha , Sahu Abhiram 
Published: June 2003

AbstractUsing a rat model of chronic central leptin infusion in which neuropeptide Y neurons develop leptin resistance, we examined whether leptin signal transduction mechanism in the hypothalamus is altered during central leptin infusion. Adult male rats were infused chronically into the lateral cerebroventricle with leptin (160 ng/h) or vehicle via Alzet pumps for 16 d. In the leptin-infused group, the initial decrease in food intake was followed by a recovery to their preleptin levels by d 16, although food intake remained significantly lower than in artificial cerebrospinal fluid controls; and body weight gradually decreased reaching a nadir at d 11 and remained stabilized at lower level thereafter. Phosphorylated leptin receptor and phosphorylated signal transducer and activator of transcription-3 (p-STAT3) remained elevated in association with a sustained elevation in DNA-binding activity of STAT3 in the hypothalamus throughout 16-d period of leptin infusion. However, phosphorylated Janus kinase-2 was increased during the early part of leptin infusion but remained unaltered on d 16. Although hypothalamic suppressors of cytokine signaling-3 (SOCS3) mRNA levels were increased throughout leptin infusion, SOCS3 protein levels were increased only on d 16. This study demonstrates a sustained elevation in hypothalamic leptin receptor signaling through Janus kinase-STAT pathway despite an increased expression of SOCS3 during chronic central leptin infusion. We propose that an alteration in leptin signaling in the hypothalamus through pathways other than STAT3 and/or a defect in downstream of STAT3 signaling may be involved in food intake recovery seen after an initial decrease during chronic central leptin infusion.