bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regional Climate Simulations over North America: Interaction of Local Processes with Improved Large-Scale Flow
Authors: Miguez-Macho Gonzalo , Stenchikov Georgiy L. , Robock Alan 
Published: April 2005

Abstract
The reasons for biases in regional climate simulations were investigated in an attempt to discern whether they arise from deficiencies in the model parameterizations or are due to dynamical problems. Using the Regional Atmospheric Modeling System (RAMS) forced by the National Centers for Environmental Prediction–National Center for Atmospheric Research reanalysis, the detailed climate over North America at 50-km resolution for June 2000 was simulated. First, the RAMS equations were modified to make them applicable to a large region, and its turbulence parameterization was corrected. The initial simulations showed large biases in the location of precipitation patterns and surface air temperatures. By implementing higher-resolution soil data, soil moisture and soil temperature initialization, and corrections to the Kain–Fritch convective scheme, the temperature biases and precipitation amount errors could be removed, but the precipitation location errors remained. The precipitation location biases could only be improved by implementing spectral nudging of the large-scale (wavelength of 2500 km) dynamics in RAMS. This corrected for circulation errors produced by interactions and reflection of the internal domain dynamics with the lateral boundaries where the model was forced by the reanalysis.
MRI R2 and R2* mapping accurately estimates hepatic iron concentration in transfusion-dependent thalassemia and sickle cell disease patients
Authors: Wood John C. , Enriquez Cathleen , Ghugre Nilesh , Tyzka J. Michael , Carson Susan , Nelson Marvin D. , Coates Thomas D. 
Published: April 2005

AbstractMeasurements of hepatic iron concentration (HIC) are important predictors of transfusional iron burden and long-term outcome in patients with transfusion-dependent anemias. The goal of this work was to develop a readily available, noninvasive method for clinical HIC measurement. The relaxation rates R2 (1/T2) and R2* (1/T2*) measured by magnetic resonance imaging (MRI) have different advantages for HIC estimation. This article compares noninvasive iron estimates using both optimized R2 and R2* methods in 102 patients with iron overload and 13 controls. In the iron-overloaded group, 22 patients had concurrent liver biopsy. R2 and R2* correlated closely with HIC (r2 ≥ .95) for HICs between 1.33 and 32.9 mg/g, but R2 had a curvilinear relationship to HIC. Of importance, the R2 calibration curve was similar to the curve generated by other researchers, despite significant differences in technique and instrumentation. Combined R2 and R2* measurements did not yield more accurate results than either alone. Both R2 and R2* can accurately measure hepatic iron concentration throughout the clinically relevant range of HIC with appropriate MRI acquisition techniques. (Blood. 2005;106:1460-1465)
Chemokine up-regulation in SARS-coronavirus–infected, monocyte-derived human dendritic cells
Authors: Law Helen K. W. , Cheung Chung Yan , Ng Hoi Yee , Sia Sin Fun , Chan Yuk On , Luk Winsie , Nicholls John M. , Peiris J. S. Malik , Lau Yu Lung 
Published: April 2005

AbstractLymphopenia and increasing viral load in the first 10 days of severe acute respiratory syndrome (SARS) suggested immune evasion by SARS-coronavirus (CoV). In this study, we focused on dendritic cells (DCs) which play important roles in linking the innate and adaptive immunity. SARS-CoV was shown to infect both immature and mature human monocyte-derived DCs by electron microscopy and immunofluorescence. The detection of negative strands of SARS-CoV RNA in DCs suggested viral replication. However, no increase in viral RNA was observed. Using cytopathic assays, no increase in virus titer was detected in infected DCs and cell-culture supernatant, confirming that virus replication was incomplete. No induction of apoptosis or maturation was detected in SARS-CoV–infected DCs. The SARS-CoV–infected DCs showed low expression of antiviral cytokines (interferon α [IFN-α], IFN-β, IFN-γ, and interleukin 12p40 [IL-12p40]), moderate up-regulation of proinflammatory cytokines (tumor necrosis factor α [TNF-α] and IL-6) but significant up-regulation of inflammatory chemokines (macrophage inflammatory protein 1α [MIP-1α], regulated on activation normal T cell expressed and secreted [RANTES]), interferon-inducible protein of 10 kDa [IP-10], and monocyte chemoattractant protein 1 [MCP-1]). The lack of antiviral cytokine response against a background of intense chemokine up-regulation could represent a mechanism of immune evasion by SARS-CoV.
Infection of human CD34+ progenitor cells with Bartonella henselae results in intraerythrocytic presence of B henselae
Authors: Mändle Tanja , Einsele Hermann , Schaller Martin , Neumann Diana , Vogel Wichard , Autenrieth Ingo B. , Kempf Volkhard A. J. 
Published: April 2005

AbstractAlthough there is evidence that endothelial cells are important targets for human pathogenic Bartonella species, the primary niche of infection is unknown. Here we elucidated whether human CD34+ hematopoietic progenitor cells (HPCs) internalize B henselae and may serve as a potential niche of the pathogen. We showed that B henselae does not adhere to or invade human erythrocytes. In contrast, B henselae invades and persists in HPCs as shown by gentamicin protection assays, confocal laser scanning microscopy (CLSM), and electron microscopy (EM). Fluorescence-activated cell sorting (FACS) analysis of glycophorin A expression revealed that erythroid differentiation of HPCs was unaffected following infection with B henselae. The number of intracellular B henselae continuously increased over a 13-day period. When HPCs were infected with B henselae immediately after isolation, intracellular bacteria were subsequently detectable in differentiated erythroid cells on day 9 and day 13 after infection, as shown by CLSM, EM, and FACS analysis. Our data provide, for the first time, evidence that a bacterial pathogen is able to infect and persist in differentiating HPCs, and suggest that HPCs might serve as a potential primary niche in Bartonella infections.
[18F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) in aggressive lymphoma: an early prognostic tool for predicting patient outcome
Authors: Haioun Corinne , Itti Emmanuel , Rahmouni Alain , Brice Pauline , Rain Jean-Didier , Belhadj Karim , Gaulard Philippe , Garderet Laurent , Lepage Eric , Reyes Felix , Meignan Michel 
Published: April 2005

AbstractAssessment of early therapeutic response using metabolic imaging is potentially useful to determine prognosis in aggressive lymphoma. Between January 2000 and January 2004, 90 patients with newly diagnosed aggressive lymphoma (median age 53 years, 94% diffuse large B-cell) were prospectively explored with [18F]fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) prior to induction chemotherapy, after 2 cycles (“early PET”), and after induction completion. Therapeutic response was evaluated using conventional diagnostic methods at 4 cycles. Induction treatment with an anthracycline-containing regimen was administered to all patients, associated with rituximab in 41%. According to the International Prognostic Index (IPI), 37 patients and 53 patients belonged to the lower- and higher-risk groups, respectively. At midinduction, “early PET” was considered negative in 54 patients and positive in 36. After completion of induction, 83% of PET-negative patients achieved complete remission compared with only 58% of PET-positive patients. Outcome differed significantly between PET-negative and PET-positive groups; the 2-year estimates of event-free survival reached 82% and 43%, respectively (P &lt; .001), and the 2-year estimates of overall survival reached 90% and 61%, respectively (P = .006). Predictive value of “early PET” was observed in both the lower-risk and higher-risk groups, indicating prognostic independence from the IPI. Therefore, FDG-PET should be an early guide to first-line strategies in aggressive lymphoma. (Blood. 2005;106:1376-1381)
Identification of 2 major loci linked to autoimmune hemolytic anemia in NZB mice
Authors: Kikuchi Shuichi , Amano Hirofumi , Amano Eri , Fossati-Jimack Liliane , Santiago-Raber Marie-Laure , Moll Thomas , Ida Akinori , Kotzin Brian L. , Izui Shozo 
Published: April 2005

AbstractUsing a cohort of C57BL/6 (B6) × (NZB × B6)F1 backcross male mice bearing the Yaa (Y-linked autoimmune acceleration) mutation, we mapped and characterized the NZB-derived susceptibility loci predisposing to the development of autoimmune hemolytic anemia (AHA). Our analysis identified 2 major loci on NZB chromosome 7 and chromosome 1 linked with Coombs antierythrocyte autoantibody production, and their contributions were confirmed by the analysis of B6.Yaa mice (B6 mice bearing the Yaa mutation) congenic for each NZB-derived susceptibility interval. A newly identified Aia3 (autoimmune anemia 3) locus present on NZB chromosome 7 selectively regulated Coombs antibody responses, while the second locus, directly overlapping with Nba2 (NZB autoimmunity 2) on chromosome 1, promoted the development of AHA, likely as part of its effect on overall production of lupus autoantibodies. A higher incidence of Coombs antibody production in B6.Aia3 congenic mice (B6 mice bearing the NZB-Aia3 locus) than B6.Nba2 mice (B6 mice bearing the NZB-Nba2 locus) indicated a major role for Aia3 in AHA. Notably, lack of expansion of B1 cells in B6.Aia3 congenic mice argued against the involvement of this subset in AHA. Finally, our analysis of BC mice also demonstrated the presence of a B6-derived H2-linked locus on chromosome 17 that apparently regulated the production of Coombs antibodies as a result of its overall autoimmune promoting effect.
Exhaled NO may predict the decline in lung function in bronchiolitis obliterans syndrome
Authors: Brugière O. , Thabut G. , Mal H. , Marceau A. , Dauriat G. , Marrash-Chahla R. , Castier Y. , Lesèche G. , Colombat M. , Fournier M. 
Published: April 2005

Bronchiolitis obliterans syndrome (BOS) remains the leading cause of morbidity/mortality following lung transplantation. In recipients with BOS, markers predicting the decline in lung function are needed. The aim of this longitudinal study was to determine whether exhaled nitric oxide fraction (FeNO) measurements provide useful information for discriminating patients with unstable BOS from those with stable BOS.During a 14-month period, 145FeNOmeasurements were performed in 50 lung transplant recipients. Among them, 16 recipients with BOS (32FeNOmeasurements) were analysed. For eachFeNOmeasurement, the patients were classified into three groups according to the decline in forced expiratory volume in one second (FEV1) within the following 6 months: 1) stable BOS free; 2) stable BOS (decline in FEV1of <5%); and 3) unstable BOS (decline in FEV1of ≥15%).The meanFeNOin patients with unstable BOS was significantly increased compared with that in stable BOS-free patients (18.4±5.7versus9.7±3.7 ppb) and that in patients with stable BOS (18.4±5.7versus9.7±3.3 ppb).The present findings suggest that, in patients with bronchiolitis obliterans syndrome, a raised exhaled nitric oxide fraction may predict the development of worrisome functional impairment during long-term follow-up.
LPS-induced lung inflammation is linked to increased epithelial permeability: role of MLCK
Authors: Eutamene H. , Theodorou V. , Schmidlin F. , Tondereau V. , Garcia-Villar R. , Salvador-Cartier C. , Chovet M. , Bertrand C. , Bueno L. 
Published: April 2005

The respiratory system is directly exposed to low levels of lipopolysaccharide (LPS), present as a contaminant on airborne particles. In cystic fibrosis, the prevailing data identify structural changes of the airway epithelium, as well as tight junction dilatation. This study was aimed at determining the contribution of myosin light chain kinase to maintaining airway epithelium barrier integrity in the lung inflammatory response to LPS in rats.The effects of the selective myosin light chain kinase inhibitor, 5-iodonaphthalene-1-sulphonyl-homopiperazine (ML-7), were evaluated: 1) on pulmonary inflammation and airway epithelium barrier permeability alterations induced by intra-tracheal LPS fromPseudomonas aeruginosa; and 2) on levels of the phosphorylated form of the myosin light chain, which is increased in a human airway epithelial cell line (NCI-H292) and tracheal tissue after LPS exposure.The results show that LPS increased airway epithelium barrier paracellular permeability and lung inflammation, and that pre-treatment with ML-7 inhibited both effects. This effect of ML-7 was associated with the inhibition of phosphorylated myosin light chain in both NCI-H292 cells and tracheal tissue.The data, obtained usingin vivoandin vitroapproaches, demonstrate a key role for myosin light chain kinase in lung inflammation, and suggest that myosin light chain kinase could be a potential target for novel drugs intended for relief of lung injury.
The inositol trisphosphate pathway mediates platelet-activating-factor-induced pulmonary oedema
Authors: Göggel R. , Uhlig S. 
Published: April 2005

Platelet-activating factor (PAF) is a pro-inflammatory lipid mediator that increases vascular permeability by simultaneous activation of two pathways, one dependent on the cyclooxygenase metabolite prostaglandin E2and the other on the sphingomyelinase metabolite ceramide. The hypothesis that part of the PAF-induced oedema is mediatedviathe inositol 1,4,5-trisphosphate (IP3) pathway or Rho kinase pathway was investigated.Oedema formation was induced in isolated perfused rat lungs by injection of 5 nmol PAF into the pulmonary artery. Lungs were pre-treated with specific inhibitors: edelfosine (L108) to block phosphatidyl-inositol-specific phospholipase C, xestospongin to block the IP3receptor, 5-iodonaphthalene-1-sulphonyl-homopiperazine (ML-7) to block myosin light chain kinase, and (+)-R-trans-4-(aminoethyl)-N-(4-pyridyl)cyclohexanecarboxamide (Y27632) to block Rho-associated protein kinase.Pre-treatment with L108 or xestospongin reduced PAF-induced oedema formation by 58 and 56%, respectively. The effect of L108 was additive to that of the cyclooxygenase inhibitor acetyl salicylic acid (88% oedema reduction). PAF-induced oedema formation was also reduced if extracellular calcium concentrations were lowered. Furthermore, treatment with ML-7 reduced oedema formation by 54%, whereas Y27632 was without effect.It is concluded that platelet-activating-factor-triggered oedema is mediated by activation of the inositol 1,4,5-trisphosphate pathway, influx of extracellular calcium and subsequent activation of a myosin light chain kinase-dependent and Rho-associated-protein-kinase-independent mechanism.
Increased expression of p38 MAPK in human bronchial epithelium after lipopolysaccharide exposure
Authors: Roos-Engstrand E. , Wallin A. , Bucht A. , Pourazar J. , Sandström T. , Blomberg A. 
Published: April 2005

Bacterial endotoxin (lipopolysaccharides (LPS)) is normally present in the wall of Gram-negative bacteria and has potent pro-inflammatory properties. Exposure to LPS has been shown to induce neutrophilic airway inflammation in humans. The aim of this investigation was to study the early inflammatory responses to LPS exposure in human airway mucosain vivo.In total, 15 healthy nonsmoking volunteers participated. Bronchoscopy was performed on two separate occasions, 3 h after saline inhalation and after inhalation of 50 μg LPS in saline. Endobronchial mucosal biopsy specimens were taken and stained immunohistochemically using a panel of monoclonal antibodies directed against mitogen-activated protein kinases (MAPKs), transcription factors, cytokines, adhesion molecules and inflammatory cells.Expression of p38 MAPK increased as a consequence of LPS exposure, as determined by both total epithelial staining and nuclear location. These two responses were strongly associated. Epithelial expression of interleukin-8 showed a tendency towards a significant increase after LPS compared to saline. Epithelial mast cell numbers were increased after LPS, whereas neutrophil numbers were unchanged.Inhalation of lipopolysaccharide induced activation of the bronchial epithelium, as demonstrated 3 h after exposure by increased expression of p38 mitogen-activated protein kinase and interleukin-8, and may represent early regulatory steps in the subsequent development of a neutrophilic bronchial inflammation.
Significance of positiveStenotrophomonas maltophiliaculture in acute respiratory tract infection
Authors: Pathmanathan A. , Waterer G. W. 
Published: April 2005

Stenotrophomonas maltophiliais a common coloniser of the respiratory tract of patients with chronic lung disease, and, in the absence of pneumonia or bacteraemia, is often ignored by physicians at the Royal Perth Hospital (Perth, Australia). Experience at the Royal Perth Hospital was reviewed to determine whether ignoringS. maltophiliain this setting has any apparent effect on clinical outcome.All patients who presented with an acute respiratory illness and yielded a positive culture forS. maltophiliabetween 1995 and 2002 were retrospectively reviewed. All subjects had to yield a positive respiratory isolate ofS. maltophiliaand undergo chest radiography within 24 h of the isolate being obtained.Ninety-two episodes were identified in 89 individuals; 64 showed no evidence of consolidation. Of the study group, 51 (80.0%) received no anti-S. maltophiliaantibiotic therapy and 21 (32.8%) had a nosocomially acquired isolate. The overall mortality rate was 20.3%. There was no impact of anti-S. maltophiliatherapy on outcome. The only independent predictor of mortality was serum albumin level.As there was no measurable impact of antibiotic therapy, in the absence of consolidation, a positive respiratory tract isolate ofStenotrophomonas maltophiliaprobably represents colonisation of a severely impaired host rather than invasive disease.
Standardised mortality rates in females and males with COPD and asthma
Authors: Ringbaek T. , Seersholm N. , Viskum K. 
Published: April 2005

Mortality studies of males and females with chronic obstructive pulmonary disease (COPD) and asthma have suggested that females have a poorer prognosis than males, but the results are either not unanimous or based on poorly characterised patients. The current study analysed the mortality of 279 asthma patients and 869 COPD patients, who were seeking pension due to disability, and compared mortality rates with expected rates derived from the general population.The mean follow-up period was 13.3 yrs (range 2.5–22.4 yrs) during which time 96 (34.4%) and 671 (77.2%) deaths were identified among asthma and COPD patients, respectively. The average age at study entry was 46.8 and 56.6 yrs, and the average forced expiratory volume in one second (FEV1) was 68.8 and 44.1 % predicted in the two diagnostic groups. After adjustment for predictors of survival (age, FEV1% predicted, chronic bronchitis, body mass index, smoking status, oral prednisolone, ischaemic heart disease, and cor pulmonale), the relative risk of death was 1.21 (95% confidence interval: 0.77–1.89) and 0.98 (0.83–1.16) in females compared with males, in asthma and COPD patients, respectively.The standardised mortality rate (SMR) for males was 1.54 (1.10–2.09) and 2.7 (2.5–3.0), and for females 1.91 (1.44–2.49) and 4.8 (4.2–5.4), in asthma and COPD patients, respectively. Direct comparison of the SMR of males and females showed that females had higher mortality than males, with a rate ratio of 1.24 (0.82–1.84) and 1.8 (1.5–2.0), in asthma and COPD patients, respectively. Poisson regression analysis with control for the confounders did not change this result.Females and males with the same level of obstructive lung disease appear to have the same level of mortality. However, using standardised mortality rates, females have a higher mortality than males, suggesting that the protective effect of being female is lost in chronic obstructive pulmonary disease patients.
Effects of salbutamol and enantiomers on allergen-induced asthmatic reactions and airway hyperreactivity
Authors: Westerhof F. J. , Zuidhof A. B. , Kok L. , Meurs H. , Zaagsma J. 
Published: April 2005

Salbutamol consists of a racemic mixture ofR- andS-salbutamol.R-salbutamol (levalbuterol) is the active bronchodilating enantiomer, whereasS-salbutamol is thought to be pharmacologically inactive or to exert adverse effects.This study evaluated the bronchoprotective effects of inhalation of therapeutically relevant doses of the racemate and individual enantiomers in guinea pigs.It was found that basal airway reactivity to histamine was similarly reduced 30 min after inhalation of equivalent doses ofRS- andR-salbutamol; this protective effect disappeared within 3 h. Inhalation ofRS- andR-salbutamol 30 min before and 5.5 h after allergen challenge suppressed allergen-induced airway hyperreactivity to histamine after the early and late asthmatic reaction, completely inhibiting the early asthmatic reaction and tending to reduce the development of the late asthmatic reaction. At 5 h after allergen challenge, the inhibition of airway hyperreactivity was more pronounced in animals treated withR-salbutamol compared to racemate-treated animals. Both basal airway reactivity and allergen–induced hyperreactivity were not affected byS-salbutamol. Inflammatory cell infiltration was not affected by the racemate or the individual enantiomers.In conclusion, inhalation of therapeutically relevant doses ofR- andRS-salbutamol effectively suppress allergen-induced airway reactivity after the early and late asthmatic reactions, theR-enantiomer being slightly more potent with respect to early airway reactivity than the racemate. No adverse effects were observed for theS-enantiomer.
The effects of body weight on airway calibre
Authors: King G. G. , Brown N. J. , Diba C. , Thorpe C. W. , Muñoz P. , Marks G. B. , Toelle B. , Ng K. , Berend N. , Salome C. M. 
Published: April 2005

Increased wheeze and asthma diagnosis in obesity may be due to reduced lung volume with subsequent airway narrowing.Asthma (wheeze and airway hyperresponsiveness), functional residual capacity (FRC) and airway conductance (Gaw) were measured in 276 randomly selected subjects aged 28–30 yrs. Data were initially adjusted for smoking and asthma before examining relationships between weight and FRC (after adjustment for height), and between body mass index (BMI = weight·height−2) andGaw(after adjustment for FRC) by multiple linear regression, separately for females and males.For males and females, BMI (±95% confidence interval) was 27.0±4.6 kg·m−2and 25.6±6.0 kg·m−2respectively,Gawwas 0.64±0.04 L·s−1·cmH2O−1and 0.57±0.03 L·s−1·cmH2O−1, and FRC was 85.3±3.4 and 84.0±2.9% of predicted. Weight correlated independently with FRC in males and females. BMI correlated independently and inversely withGawin males, but only weakly in females.In conclusion, obesity is associated with reduced lung volume, which is linked with airway narrowing. However, in males, airway narrowing is greater than that due to reduced lung volume alone. The mechanisms causing airway narrowing and sex differences in obesity are unknown.