bluuebunny/crossref_metadata_2025_split huggingface dataset:
Maintaining the self-renewal and differentiation potential of human CD34+ hematopoietic cells using a single genetic element
Authors: Mulloy James C. , Cammenga Jorg , Berguido Francisco J. , Wu Kaida , Zhou Ping , Comenzo Raymond L. , Jhanwar Suresh , Moore Malcolm A. S. , Nimer Stephen D. 
Published: September 2003

AbstractHematopoiesis is a complex process involving hematopoietic stem cell (HSC) self-renewal and lineage commitment decisions that must continue throughout life. Establishing a reproducible technique that allows for the long-term ex vivo expansion of human HSCs and maintains self-renewal and multipotential differentiation will allow us to better understand these processes, and we report the ability of the leukemia-associated AML1-ETO fusion protein to establish such a system. AML1-ETO-transduced human CD34+ hematopoietic cells routinely proliferate in liquid culture for more than 7 months, remain cytokine dependent for survival and proliferation, and demonstrate self-renewal of immature cells that retain both lymphoid and myeloid potential in vitro. These cells continue to express the CD34 cell surface marker and have ongoing telomerase activity with maintenance of telomere ends, however they do not cause leukemia in nonobese diabetic-severe combined immunodeficiency (NOD/SCID) mice. Identification of the signaling pathways that are modulated by AML1-ETO and lead to the self-renewal of immature human progenitor cells may assist in identifying compounds that can efficiently expand human stem and progenitor cells ex vivo. (Blood. 2003; 102:4369-4376)
Up-regulation of SLAP in FLI-1-transformed erythroblasts interferes with EpoR signaling
Authors: Lebigot Ingrid , Gardellin Paola , Lefebvre Laurent , Beug Hartmut , Ghysdael Jacques , Quang Christine Tran 
Published: September 2003

AbstractRearrangement of the FLI-1 locus and ensuing overexpression of FLI-1 protein is an early event in Friend murine leukemia virus (F-MuLV)-induced erythroleukemia. When overexpressed in primary erythroblasts, FLI-1 converts erythropoietin (Epo)-induced terminal differentiation into a proliferative response. We found that SLAP, a gene encoding a recently described negative regulator of T-cell antigen receptor function during thymocyte development, is up-regulated both at the RNA and protein levels in FLI-1-transformed erythroblasts. Src-like adaptor protein (SLAP) was found in a specific complex with erythropoietin receptor (EpoR), a cytokine receptor essential to erythroid differentiation. Constitutive expression of SLAP severely impairs hemoglobinization and late survival during Epo-induced terminal differentiation of erythroblasts. This impairment is associated with the specific inhibition of several critical Epo-dependent signaling events, including signal transducer and activator of transcription 5 (STAT5) activation and up-regulation of the expression of the antiapoptotic BCL-X gene. Our data support a model by which FLI-1 inhibits normal erythroid differentiation through the deregulation of genes encoding adaptors/effectors that modify the signaling output of cytokine receptors normally required for terminal differentiation. (Blood. 2003; 102:4555-4562)
Acute graft-versus-host disease in patients with Fanconi anemia or acquired aplastic anemia undergoing bone marrow transplantation from HLA-identical sibling donors: risk factors and influence on outcome
Authors: Guardiola Philippe , Socié Gérard , Li Xiaxin , Ribaud Patricia , Devergie Agnès , Espérou Hélène , Richard Patrice , Traineau Richard , Janin Anne , Gluckman Eliane 
Published: September 2003

Abstract
To assess whether Fanconi anemia (FA) patients might be at risk for acute graft-versus-host disease (AGvHD) despite using low-intensity conditionings, we retrospectively analyzed the incidence of AGvHD and its impact on outcome in 37 FA patients and 73 patients with acquired aplastic anemia (AAA) that received transplants at Saint Louis Hospital from HLA-genotypic identical siblings with similar conditionings (thoraco-abdominal irradiation plus cyclophosphamide 20 [FA] or 150 mg/kg [AAA]). Despite being younger, FA patients had an increased risk of grades II to IV AGvHD (relative risk [RR], 2.00; P = .021), especially in younger patients (RR, 7.93; P = .014). The risks of requiring systemic corticosteroids to treat AGvHD and experiencing cortico-resistant AGvHD were significantly increased in FA patients. Although non-FA and FA patients had similar 10-year outcomes, acute and chronic GvHD had a biphasic effect on FA patient outcome with an additional cluster of lethal events starting by 5 years after transplantation. This late survival fall, restricted to FA patients, was closely related to head and neck carcinomas (15-year incidence: 53%). FA patients represent a group at risk regarding AGvHD when using irradiation-based conditionings. The impact of AGvHD on survival may not be limited to the early posttransplantation period and may be a major risk factor for head and neck carcinomas and late mortality in FA patients.
IL-10 regulates plasmacytoid dendritic cell response to CpG-containing immunostimulatory sequences
Authors: Duramad Omar , Fearon Karen L. , Chan Jean H. , Kanzler Holger , Marshall Jason D. , Coffman Robert L. , Barrat Franck J. 
Published: September 2003

AbstractImmunostimulatory sequences (ISS) are short oligonucleotides containing unmethylated cytosine-phosphate-guanine (CpG) dinucleotides that stimulate innate immune responses through Toll-like receptor-9 on B cells and plasmacytoid dendritic cell (PDC) precursors. The anti-inflammatory cytokine interleukin (IL)-10 is predicted to be a potent inhibitor of many of the activities described for ISS, and this may impact the use of ISS in disease states characterized by elevated IL-10. As the activities of ISS on PDCs are central to many clinical applications of ISS, we have studied the effects of IL-10 on PDC stimulation by 3 distinct classes of ISS. IL-10 inhibited cytokine production and survival of ISS-activated PDCs; however, IL-12 induction was much more sensitive to inhibition than interferon (IFN)-α induction. Within the PDC population are cells that respond to ISS by producing either IL-12 or IFN-α but not both cytokines. IL-12-producing PDCs require costimulation through CD40 and appear more mature than IFN-α-producing PDCs. The 3 distinct classes of ISS differed with respect to induction of PDC maturation and T-cell priming capacity. IL-10 regulated PDC activation but did not inhibit the subsequent T-cell-priming ability of PDCs already activated by ISS. (Blood. 2003;102:4487-4492)
Does the tube-compensation function of two modern mechanical ventilators provide effective work of breathing relief?
Authors: Maeda Yoshiko , Fujino Yuji , Uchiyama Akinori , Taenaka Nobuyuki , Mashimo Takashi , Nishimura Masaji 
Published: August 2003

Abstract
Objective
An endotracheal tube (ETT) imposes work of breathing on mechanically ventilated patients. Using a bellows-in-a-box model lung, we compared the tube compensation (TC) performances of the Nellcor Puritan-Bennett 840 ventilator and of the Dräger Evita 4 ventilator.

Measurements and results
Each ventilator was connected to the model lung. The respiratory rate of the model lung was set at 10 breaths/min with 1 s inspiratory time. Inspiratory flows were 30 or 60 l/min. A full-length 8 mm bore ETT was inserted between the ventilator circuit and the model lung. The TC was set at 0%, 10%, 50%, and 100% for both ventilators. Pressure was monitored at the airway, the trachea, and the pleura, and the data were recorded on a computer for later analysis of the delay time, of the inspiratory trigger pressure, and of the pressure–time product (PTP). The delay time was calculated as the time between the start of inspiration and minimum airway pressure, and the inspiratory trigger pressure was defined as the most negative pressure level. The same measurements were performed under pressure support ventilation of 4 and 8 cmH2O.
The PTP increased according to the magnitude of inspiratory flow. Even with 100% TC, neither ventilator could completely compensate for the PTP imposed by the ETT. At 0% TC the PTP tended to be less with the Nellcor Puritan-Bennett 840 ventilator, while at 100% TC the PTP tended to be less with the Dräger Evita 4 ventilator. A small amount of pressure support can be equally effective to reduce the inspiratory effort compared with the TC.

Conclusion
Although both ventilators provided effective TC, even when set to 100% TC they could not entirely compensate for a ventilator and ETT-imposed work of breathing. The effect of TC is less than that of pressure support ventilation. Physicians should be aware of this when using TC in weaning trials.
Comparison of sufentanil with sufentanil plus magnesium sulphate for sedation in the intensive care unit using bispectral index
Authors: Memiş Dilek , Turan Alparslan , Karamanlıoğlu Beyhan , Oğuzhan Nihal , Pamukçu Zafer 
Published: August 2003

Abstract
Introduction
In intensive care unit patients we assessed, using bispectral index (BIS) monitoring, whether the addition of magnesium sulphate infusion could decrease the sufentanil infusion required to maintain sedation.

Patients and methods
A total of 30 adult patients who were expected to require machanical ventilation for 6 hours in the intensive care unit were randomly assigned to receive either sufentanil infusion or sufentanil plus magnesium infusion. We monitored BIS levels continously. BIS levels in the range 61–88 are required to maintain a state of sedation, and in both groups BIS levels were kept within this range by increasing or decreasing the sufentanil infusion. Hourly consumption of sufentanil was monitored. Cardiovascular, respiratory and biochemical data were recorded.

Results
There was no significant difference between the groups with respect to cardiovascular, respiratory and biochemical parameters. Magnesium infusion, when added to sufentanil infusion, decreased the consumption of sufentanil at all times accept during the first hour (P < 0.001). There was no significant difference in BIS values between the groups (P > 0.05).

Conclusion
This is the first clinical study to demonstrate that magnesium sulphate infusion decreases sufentanil requirements. Because of the limited number of patients included and the short period of observation, our findings must be confirmed by larger clinical trials of magnesium infusion titrated to achieve prespecified levels of sedation. Furthermore, randomized clinical studies are needed to determine the effects of magnesium infusion on opioids.
Estimation of energy requirements for mechanically ventilated, critically ill patients using nutritional status
Authors: Kan Mee-Nin , Chang Han-Hsin , Sheu Woei-Fen , Cheng Chien-Hsiang , Lee Bor-Jen , Huang Yi-Chia 
Published: August 2003

Abstract
Background
There is very little information on what is considered an adequate energy intake for mechanically ventilated, critically ill patients. The purpose of the present study was to determine this energy requirement by making use of patients' nutritional status.

Methods
The study was conducted in a multidisciplinary intensive care unit of Taichung Veterans General Hospital, Taiwan. Patients were hemodynamically stable and not comatose, and were requiring at least 7 days of mechanical ventilation. Fifty-four patients successfully completed this study. The resting energy expenditure was measured using indirect calorimetry. The total energy requirement was considered 120% of the measured energy expenditure. The daily nutrient intake was recorded. Nutritional status was assessed using single and multiple parameters, nitrogen balance, and medical records, and was performed within 24 hours of admission and after 7 days in the intensive care unit.

Results
Fifteen patients were being underfed (<90% of total energy requirement), 20 patients were in the appropriate feeding (AF) group (within ± 10% of total energy requirement), and 19 patients received overfeeding (>110% of total energy requirement). Patients in the underfeeding group received only 68.3% of their energy requirement, while the overfeeding group patients received up to 136.5% of their required calories. Only patients in the AF group had a positive nitrogen balance (0.04 ± 5.1) on day 7. AF group patients had a significantly higher Nutritional Risk Index value at day 7 than at day 1.

Conclusion
AF patients had more improvement in nutritional status than patients in the other feeding groups. To provide at least 120% of the resting energy expenditure seemed adequate to meet the caloric energy needs of hemodynamically stable, mechanically ventilated, critically ill patients.
Assessment of six mortality prediction models in patients admitted with severe sepsis and septic shock to the intensive care unit: a prospective cohort study
Authors: Arabi Yaseen , Shirawi Nehad Al , Memish Ziad , Venkatesh Srinivas , Al-Shimemeri Abdullah 
Published: August 2003

Abstract
Introduction
We conducted the present study to assess the validity of mortality prediction systems in patients admitted to the intensive care unit (ICU) with severe sepsis and septic shock. We included Acute Physiology and Health Evaluation (APACHE) II, Simplified Acute Physiology Score (SAPS) II, Mortality Probability Model (MPM) II0 and MPM II24 in our evaluation. In addition, SAPS II and MPM II24 were customized for septic patients in a previous study, and the customized versions were included in this evaluation.

Materials and method
This cohort, prospective, observational study was conducted in a tertiary care medical/surgical ICU. Consecutive patients meeting the diagnostic criteria for severe sepsis and septic shock during the first 24 hours of ICU admission between March 1999 and August 2001 were included. The data necessary for mortality prediction were collected prospectively as part of the ongoing ICU database. Predicted and actual mortality rates, and standardized mortality ratio were calculated. Calibration was assessed using Lemeshow–Hosmer goodness of fit C-statistic. Discrimination was assessed using receiver operating characteristic curves.

Results
The overall mortality prediction was adequate for all six systems because none of the standardized mortality ratios differed significantly from 1. Calibration was inadequate for APACHE II, SAPS II, MPM II0 and MPM II24. However, the customized version of SAPS II exhibited significantly improved calibration (C-statistic for SAPS II 23.6 [P = 0.003] and for customized SAPS II 11.5 [P = 0.18]). Discrimination was best for customized MPM II24 (area under the receiver operating characteristic curve 0.826), followed by MPM II24 and customized SAPS II.

Conclusion
Although general ICU mortality system models had accurate overall mortality prediction, they had poor calibration. Customization of SAPS II and, to a lesser extent, MPM II24 improved calibration. The customized model may be a useful tool when evaluating outcomes in patients with sepsis.
Tissue expression of copines and isolation of copines I and III from the cytosol of human neutrophils
Authors: Cowland Jack B , Carter Daniel , Bjerregaard Malene D , Johnsen Anders H , Borregaard Niels , Lollike Karsten 
Published: August 2003

Abstract
Copines are a recenty identified group of proteins characterized by two Ca2+-binding C2-domains at the N terminus and an A-domain at the C terminus. Although pEST sequences indicate the existence of at least seven copines in man, only copines I, III, and VI have been identified at protein level. Here, we describe the isolation of copines I and III in the cytosol of human neutrophils by use of Ca2+-induced hydrophobic chromatography. This is the first demonstration that copines are coexpressed in the same cell. We found that copine III exists in the cytosol of human neutrophils as a monomer with a blocked N terminus. Copines I and III undergo conformational changes upon Ca2+ binding that lead to exposure of hydrophobic patches. Examination of RNA from 68 human tissues demonstrated that copines I–III are ubiquitously expressed whereas copines IV–VII each has a more restricted and individual expression profile. Expression of copines I–III was also demonstrated in neutrophil precursors from bone marrow. Copine I was uniformly expressed at all stages of neutrophil differentiation, whereas copine II and even more so, copine III were expressed in the more immature neutrophil precursors, which indicates an individual function of these copines.
Cross-talk between regulators of myeloid development: C/EBPα binds and activates the promoter of the PU.1 gene
Authors: Kummalue Tanawan , Friedman Alan D 
Published: August 2003

Abstract
CCAAT/enhancer-binding protein (C/EBP)α and PU.1 are required for myelopoiesis. Examination of the murine PU.1 promoter revealed several potential C/EBP-binding sites. Gel-shift assay demonstrated that C/EBPα expressed in 293T cells bound the site centered at –68 most potently. C/EBPα from 32D cl3 myeloid cell nuclear extracts also bound this site strongly, and endogenous C/EBPβ did so to a lesser extent, whereas these C/EBP isoforms bound the neutrophil elastase promoter with equal affinity. The –68 site in the murine PU.1 promoter is conserved in the human PU.1 promoter. Mutation of the –68 C/EBP-binding site in a −85/+152 promoter segment linked to the luciferase cDNA reduced promoter activity fourfold in 293T cells in the presence of cotransfected C/EBPα and twofold in 32D cl3 myeloid cells. Induction of endogenous PU.1 RNA by C/EBPα-estradiol receptor (ER) in the presence of cycloheximide is obviated by mutation of the C/EBPα DNA-binding domain, and chromosomal immunoprecipitation demonstrated specific interaction of C/EBPα and C/EBPα-ER with the PU.1 promoter. Finally PU.1 RNA is reduced several-fold in immortalized C/EBPα (−/−) compared with (+/−) cells. Together, these findings indicate that C/EBPα binds and activates the endogenous PU.1 gene in myeloid cells. Induction of PU.1 by C/EBPα may account for increased levels of PU.1 in myeloid as compared with B lymphoid cells and in this way, may contribute to the specification of myeloid progenitors.
Effect of 11 September 2001 on suicide and homicide in England and Wales
Authors: Salib Emad 
Published: August 2003

BackgroundThe tragic events of 11 September 2001 and televised scenes of the terrorists' homicidal and suicidal acts could have had an impact on the behaviour of some people, who harbour suicidal ideation or homicidal tendencies.AimsTo assess the effect of 11 September 2001 on the rate of suicide and homicide in England and Wales.MethodAnalysis of the number of suicides (ICD–9 codes: E950–E959), undetermined injury deaths (E980–E989) and homicides (E960–E969) in England and Wales in the 12 weeks before and after 11 September 2001 and during a similar period in the previous two years.ResultsThe number of suicides reported in the month of September 2001 was significantly lower than other months in the same year and any September of the previous 22 years in England and Wales. A suicide reduction in men, regardless of age, occurred in the week starting Tuesday 11 September 2001. A reduction in female suicide occurred during the four weeks following the attack. There was no evidence of a similar effect on homicide.ConclusionsThe tragic events of 11 September 2001 appear to have had a brief but significant inverse effect on suicide. The finding of this study supports Durkheim's theory that periods of external threat create group integration within society and lower the suicide rate through the impact on social cohesion.
Prevalence of violent victimisation in severe mental illness
Authors: Walsh Elizabeth , Moran Paul , Scott Charles , McKenzie Kwame , Burns Tom , Creed Francis , Tyrer Peter , Murray Robin M. , Fahy Tom 
Published: August 2003

BackgroundSince de-institutionalisation, much has been written about the risk posed to the community by those with severe mental illness. However, violent victimisation of people with mental illnesses has received little attention.AimsTo establish the 1-year prevalence of violent victimisation in community-dwelling patients with psychosis and to identify the socio-demographic and clinical correlates of violent victimisation.MethodA total of 691 subjects with established psychotic disorders were interviewed. The past-year prevalence of violent victimisation was estimated and compared with general population figures. Those who reported being violently victimised were compared with those who did not on a range of social and clinical characteristics.ResultsSixteen per cent of patients reported being violently victimised. Victims of violence were significantly more likely to report severe psychopathological symptoms, homelessness, substance misuse and previous violent behaviour and were more likely to have a comorbid personality disorder.ConclusionsThose with psychosis are at considerable risk of violent victimisation in the community. Victimisation experience should be recorded in the standard psychiatric interview.
A survey of consultants in the psychiatry of learning disability
Authors: Lindsey Mary , Flynn Adrian 
Published: August 2003

Aims and MethodAll 208 consultant members of the Faculty for the Psychiatry of Learning Disability were contacted and asked to complete a questionnaire to provide qualitative and quantitative information about their work and experiences.ResultsOne hundred and thirty-six consultants responded, giving a 64% response rate. They reported a wide range of clinical, academic and management skills, with 72 having registration in other specialities. Insufficient in-patient provision and problems with discharge were cited by 85% of respondents. There was a wide disparity in the provision of mental health services for children and adolescents with learning disabilities and 12 areas reported no services from any source. Although most respondents showed satisfaction with clinical work and professional relationships, there were many concerns about management, commissioning and planning of services.Clinical ImplicationsConsultant psychiatrists in the field of learning disability are a broadly skilled group of clinicians with a wide range of responsibilities and areas of expertise, but many are working in services that they see as under-resourced and poorly managed, planned and commissioned. Overall levels of satisfaction are good, particularly in relation to clinical work, peer support and study/academic work.
Alterations of Plasma Ghrelin Levels in Rats with Lipopolysaccharide-Induced Wasting Syndrome and Effects of Ghrelin Treatment on the Syndrome
Authors: Hataya Yuji , Akamizu Takashi , Hosoda Hiroshi , Kanamoto Naotetsu , Moriyama Kenji , Kangawa Kenji , Takaya Kazuhiko , Nakao Kazuwa 
Published: September 2003

AbstractGhrelin not only strongly stimulates GH secretion, but is also involved in energy homeostasis by stimulating food intake and promoting adiposity through a GH-independent mechanism. These effects of ghrelin may play an important role in the pathophysiology of inflammatory wasting syndrome, in which both the somatotropic axis and energy balance are altered. In this study we investigated plasma ghrelin concentrations after lipopolysaccharide (LPS) administration to rats, a model of the wasting syndrome and critical illness. In addition, the therapeutic potential of the antiwasting effects of ghrelin was explored using LPS-injected rats. A single LPS injection suppressed plasma ghrelin levels 6 and 12 h later. Maximal reduction was observed 12 h after LPS injection, in a dose-dependent manner. In contrast, plasma ghrelin levels were elevated after repeated LPS injections on d 2 and 5. Peripheral administration of ghrelin twice daily (10 nmol/rat) for 5 d increased body weight gain in repeated LPS-injected rats. Furthermore, both adipose tissue weight and plasma leptin concentrations were increased after ghrelin administration in these rats. In conclusion, plasma ghrelin levels are altered in LPS-injected rats, and ghrelin treatment may provide a new therapeutic approach to the wasting syndrome and critical illness.