bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stabilin-1 localizes to endosomes and the trans-Golgi network in human macrophages and interacts with GGA adaptors
Authors: Kzhyshkowska Julia , Gratchev Alexei , Martens Jan-Henning , Pervushina Olga , Mamidi Srinivas , Johansson Sophie , Schledzewski Kai , Hansen Berit , He Xiangyuan , Tang Jordan , Nakayama Kazuhisa , Goerdt Sergij 
Published: September 2004

AbstractStabilin-1 and stabilin-2 constitute a novel family of fasciclin domain-containing hyaluronan receptor homologues recently described by us. Whereas stabilin-1 is expressed in sinusoidal endothelial cells and in macrophages in vivo, stabilin-2 is absent from the latter. In the present study, we analyzed the subcellular distribution of stabilin-1 in primary human macrophages. Using flow cytometry, expression of stabilin-1 was demonstrated on the surface of interleukin-4/dexamethasone-stimulated macrophages (MΦ2). By immunofluorescense and confocal microscopy, we established that stabilin-1 is preferentially localized in early endosome antigen-1-positive early/sorting endosomes and in recycling endosomes identified by transferrin endocytosis. Association of stabilin-1 was infrequently seen with p62 lck ligand-positive late endosomes and with CD63-positive lysosomes but not in lysosome-associated membrane protein-1-positive lysosomes. Stabilin-1 was also found in the trans-Golgi network (TGN) but not in Golgi stack structures. Glutathione S-transferase pull-down assay revealed that the cytoplasmic tail of stabilin-1 but not stabilin-2 binds to recently discovered Golgi-localized, γ-ear-containing, adenosine 5′-diphosphate-ribosylation factor-binding (GGA) adaptors GGA1, GGA2, and GGA3 long, mediating traffic between Golgi and endosomal/lysosomal compartments. Stabilin-1 did not bind to GGA3 short, which lacks a part of the Vps27p/Hrs/STAM domain. Deletion of DDSLL and LL amino acid motifs resulted in decreased binding of stabilin-1 with GGAs. A small portion of stabilin-1 colocalized with GGA2 and GGA3 in the TGN in MΦ2. Treatment with brefeldin A resulted in accumulation of stabilin-1 in the TGN. Our results suggest that stabilin-1 is involved in the GGA-mediated sorting processes at the interface of the biosynthetic and endosomal pathways; similarly to other GGA-interacting proteins, stabilin-1 may thus function in endocytic and secretory processes of human macrophages.
Population pharmacokinetics of 5-fluorouracil in colorectal cancer patients
Authors: Porta-Oltra B , Pérez-Ruixo JJ , Climente-Martí M , Merino-Sanjuán M , Almenar-Cubells D , Jiménez-Torres NV 
Published: September 2004

Aims. The pharmacokinetics of 5-fluorouracil (5-FU) after intravenous administration in color- ectal cancer patients were examined using population analysis. The relevant covariates and the extent of inter- and intraindividual variability were evaluated. Methods. Data from 27 patients with diagnosis of nonmetastatic colorectal adenocarcinoma receiving weekly 5-FU (450 mg/m2), plus levamisol 50 mg/8 hours by oral route for 3 days every 15 days, were pooled with data from 17 patients with diagnosis of metastatic colorectal adenocarcinoma, receiving daily 5-FU (425 mg/m2) and intravenous folinic acid (20 mg/m2) over five consecutive days (daily times five), every four weeks. In both groups 5-FU was administered as a 60-minute infusion and blood samples were collected at 10, 30 and 60 minutes from the end of the infusion, and analysed using a validated high-performance liquid chromatography assay. An open two-compartmental pharmacokinetic model with first-order elimination from central compartment was fitted to the plasma concentration data using nonlinear mixed effect modelling (NONMEM). The potential effect of patient covariates was evaluated using a stepwise method. Model evaluation was performed using bootstrap method. Results. The pharmacokinetic model was successfully fitted to the data. None of the covariates tested were significantly correlated to the pharmacokinetic parameters. The mean parameters’ estimates (%CV) and the percent coefficient of variation of the central tendency parameters, interindividual (IIV), interoccasion (IOV) and residual variability (s) for the final model were: CL (L/h), 65.3 (13.2); Vc (L), 14.7 (11.8); Vp (L), 334.0 (31.4); Q (L/h), 19.6 (25.5); IIVCL (%), 76.5 (34.6); IIVVc (%), 82.3 (31.0); IIVVp (%), 137.5 (35.1); IIVQ (%), 117.5 (38.5); IOVCL (%), 66.1 (45.3); IOVVc (%), 70.8 (39.5); IOVQ (%), 81.1 (27.8) and s (%), 3.0 (25.4). The bootstrap resampling method confirmed the stability of the final model. The estimates of the central tendency parameters, IIV, IOV and residual variability were essentially equal to those generated with the original dataset (0% to 18% deviation) and the 95% confidence intervals included the mean parameters’ estimates obtained from the former set. Conclusions. The two-compartmental model accurately described the pharmacokinetics of 5-FU administered by short-term infusion. A population pharmacokinetic approach is a useful tool to integrate the knowledge gathered in the clinical setting. The model developed may help in dose adaptation and will further be used in PK/PD modelling of therapeutic outcomes and adverse events.
Should CA-125 Response Criteria Be Preferred to Response Evaluation Criteria in Solid Tumors (RECIST) for Prognostication During Second-Line Chemotherapy of Ovarian Carcinoma?
Authors: Gronlund Bo , Høgdall Claus , Hilden Jørgen , Engelholm Svend A. , Høgdall Estrid V.S. , Hansen Heine H. 
Published: September 2004

Purpose The aim of the study was to compare the prognostic value of a response by the Gynecologic Cancer Intergroup (GCIG) Cancer Antigen (CA) -125 response criteria and the Response Evaluation Criteria in Solid Tumors (RECIST) on survival in patients with ovarian carcinoma receiving second-line chemotherapy. Patients and Methods From a single-institution registry of 527 consecutive patients with primary ovarian carcinoma, 131 records satisfied the inclusion criteria: ovarian carcinoma of International Federation of Gynecology and Obstetrics stage IC to IV, first-line chemotherapy with paclitaxel and a platinum compound, refractory or recurrent disease, and second-line chemotherapy consisting of topotecan or paclitaxel plus carboplatin. Univariate and multivariate analyses of survival were performed using the landmark method. Results In patients with measurable disease by RECIST and with assessable disease by the CA-125 criteria (n = 68), the CA-125 criteria were 2.6 times better than the RECIST at disclosing survival. In a multivariate Cox analysis with inclusion of nine potential prognostic parameters, CA-125 response (responders v nonresponders; hazard ratio, 0.21; P < .001) and number of relapse sites (solitary v multiple; hazard ratio, 0.47; P = .020) were identified as contributory prognostic factors for survival, whereas the parameters of RECIST (responders v nonresponders), as well as the remaining variables, had nonsignificant prognostic impact. Conclusion The GCIG CA-125 response criteria are a better prognostic tool than RECIST in second-line treatment with topotecan or paclitaxel plus carboplatin in patients with ovarian carcinoma.
Histologic Grade, But Not SYT-SSX Fusion Type, Is an Important Prognostic Factor in Patients With Synovial Sarcoma: A Multicenter, Retrospective Analysis
Authors: Guillou Louis , Benhattar Jean , Bonichon Françoise , Gallagher Gabrielle , Terrier Philippe , Stauffer Edouard , de Saint Aubain Somerhausen Nicolas , Michels Jean-Jacques , Jundt Gernot , Vince Dominique Ranchère , Taylor Sophia , Genevay Muriel , Collin Françoise , Trassard Martine , Coindre Jean-Michel 
Published: September 2004

Purpose To assess the prognostic value of SYT-SSX fusion type, in comparison with other factors, in a population of 165 patients with synovial sarcoma (SS). Patients and Methods Data on 165 patients with SS (141 with localized disease at diagnosis) were studied retrospectively. The following parameters were examined for their potential prognostic value: age at diagnosis, sex, tumor site (extremities v proximal/truncal), size, histology, mitotic count, necrosis, histologic grade (Fédération Nationale des Centres de Lutte Contre le Cancer system), stage (1997 tumor-node-metastasis system classification), surgical margin status (assessed histologically), and fusion type (SYT-SSX1 v SYT-SSX2). Median follow-up time was 37 months (range, 2 to 302 months). Results Among those patients with localized disease at diagnosis, median and 5-year disease-specific survivals (DSS) for the SYT-SSX1 and SYT-SSX2 subgroups were 126 months and 67.4% versus 82 months and 63.2%, respectively (P = .12). Median and 5-year metastasis-free survivals (MFS) were 84 months and 54.2% for SYT-SSX1 versus 50 months and 47.6% for SYT-SSX2 (P = .76). Univariate analyses showed that high histologic grade (grade 3), high mitotic count (≥ 10 mitoses/10 high-power fields), stage III disease, size greater than 7 cm, tumor necrosis, and presence of areas of poorly differentiated morphology were significant adverse prognostic factors for DSS and MFS, whereas SYT-SSX fusion type, tumor histology (biphasic v monophasic), and patient sex were not. Age greater than 35 years adversely affected DSS but not MFS. In multivariate analyses, histologic grade was the most significant prognostic factor for both DSS and MFS. Conclusion For patients with localized SS, histologic grade but not SYT-SSX fusion type is a strong predictor of survival.
Thyrotropin-Releasing Hormone-Stimulated Thyrotropin Expression Involves Islet-Brain-1/c-Jun N-Terminal Kinase Interacting Protein-1
Authors: Abe Hiroshi , Murao Koji , Imachi Hitomi , Cao Wen M. , Yu Xiao , Yoshida Kazuya , Wong Norman C. W. , Shupnik Margaret A. , Haefliger Jacques-Antoine , Waeber Gérard , Ishida Toshihiko 
Published: September 2004

Abstract
Islet-brain-1 (IB1)/c-Jun N-terminal kinase interacting protein 1 (JIP-1) is a scaffold protein that is expressed at high levels in neurons and the endocrine pancreas. IB1/JIP-1 interacts with the c-Jun N-terminal kinase and mediates the specific physiological stimuli (such as cytokines). However, the potential role of the protein in the pituitary has not been evaluated. Herein, we examined expression of the gene encoding IB1/JIP-1 and its translated product in the anterior pituitary gland and a pituitary cell line, GH3. We then examined the potential role of IB1/JIP-1 in controlling TSH-β gene expression. Exposure of GH3 cells to TRH stimulated the expression of IB1/JIP-1 protein levels, mRNA, and transcription of the promoter. The increase of IB1/JIP-1 content by transient transfection study of a vector encoding IB1/JIP-1 or by the stimulation of TRH stimulates TSH-β promoter activity. This effect is not found in the presence of a mutated nonfunctional (IB1S59N) IB1/JIP-1 protein. Together, these facts point to a central role of the IB1/JIP-1 protein in the control of TRH-mediated TSH-β stimulation.
Rapid Nongenomic Effects of 3,5,3′-Triiodo-l-Thyronine on the Intracellular pH of L-6 Myoblasts Are Mediated by Intracellular Calcium Mobilization and Kinase Pathways
Authors: D’Arezzo Silvia , Incerpi Sandra , Davis Faith B. , Acconcia Filippo , Marino Maria , Farias Ricardo N. , Davis Paul J. 
Published: September 2004

Abstractl-T3 and l-T4 activated the Na+/H+ exchanger of L-6 myoblasts, with a fast nongenomic mechanism, both in the steady state and when cells undergo acid loading with ammonium chloride. Monitored with the intracellular pH-sensitive fluorescent probe 2′,7′-bis(carboxyethyl)-5(6)-carboxyfluorescein, activation of the exchanger appeared to be initiated at the plasma membrane, because T3-agarose reproduced the effect of l-T3, and triiodothyroacetic acid, a hormone analog previously shown to inhibit membrane actions of thyroid hormone, blocked the action of l-T3 on the exchanger. We show here for the first time that transduction of the hormone signal in this nongenomic response requires tyrosine kinase-dependent phospholipase C activation and two different signaling pathways: 1) mobilization of intracellular calcium, assessed by the fluorescent probe fura-2, through activation of inositol trisphosphate receptors and without contributions from extracellular calcium or ryanodine receptors; and 2) protein phosphorylation involving protein kinase C and MAPK (ERK1/2), as shown by the use of kinase inhibitors and by immunoblotting for activated kinases.
Autumnal precipitation distribution on the southern flank of the Alps: A numerical‐model study of the mechanisms
Authors: Gheusi François , Davies Huw C. 
Published: September 2004

AbstractDuring the autumn there are frequent events of heavy precipitation on the southern slopes of the meso‐α‐scale Alpine chain. Moreover, the accompanying climatology exhibits a distinctive spatial distribution with some meso‐β‐scale regions of enhanced precipitation such as the ‘wet spot’ in the vicinity of Lago Maggiore.Possible mechanisms to account for the observed spatial distribution are established using a heuristic model‐based approach. It is shown using a mesoscale model that the response to a steady, horizontally uniform, and moisture‐laden flow impinging upon a comparatively realistic representation of the Alpine chain can reproduce both the overall meso‐α‐scale precipitation distribution and its meso‐β‐scale sub‐structure. The nature of the simulated flow regime (over, around or intermediate) is sensitive to the strength of the ambient geostrophic flow and its modification in the planetary boundary layer. Contrariwise, the simulated precipitation distribution in the Lago Maggiore ‘wet spot’ is comparatively insensitive to the changes in direction of the incident geostrophic flow from south to south‐west, and in strength in the range 10–30 m s−1, although there is a marked change in the structure of the near‐Alpine flow. This systematic precipitation enhancement appears to be related to the relative strength and compensating effects of an easterly barrier jet tracking along the zonally elongated part of the Alps and an air stream channelled between the Maritime Alps and the Apennines.Further evidence to the above interpretation of the meso‐β‐scale precipitation distribution is given with simulations conducted using a smoothed and schematic representation of the Alpine chain. Likewise, the sensitivity to the presence of a Lago Maggiore‐like indentation of the topography is tested, and evidence is provided of a further ‘indentation‐induced’ precipitation enhancement at the local scale. Copyright © 2004 Royal Meteorological Society
Flux–gradient relationship, self‐correlation and intermittency in the stable boundary layer
Authors: Klipp Cheryl L. , Mahrt Larry 
Published: September 2004

AbstractThe correlation between dimensionless shear ϕm and dimensionless height z/L, where L is the Obukhov length, for stable conditions is strongly influenced by self‐correlation for the present datasets. This effect is quite large for stronger stability but still significant for near‐neutral conditions. A conditional analysis of nocturnal stable boundary‐layer data, where ‘non‐turbulent’ parts of the record are removed, reduces the impact of nonstationarity and therefore reduces the scatter. The conditional analysis also reduces the relative importance of self‐correlation. Difficulties with estimating self‐correlation are also discussed. Copyright © 2004 Royal Meteorological Society
Sensitivity of dynamics and ozone to different representations of SSTs in the Unified Model
Authors: Braesicke P. , Pyle J. A. 
Published: September 2004

AbstractWe use a version of the Met Office Unified Model with a simple stratospheric chemistry to perform a set of multi‐annual integrations of 20 years each. The runs have different representations of ozone in the radiation and use prescribed sea surface temperatures (SSTs). In one experiment the same long‐term mean monthly mean SSTs are used each model year, whereas all other experiments use annual varying AMIP II monthly mean SSTs instead. All runs have the same simplified ozone chemistry included (regardless of which ozone is used in the radiation), so we can estimate the impact of dynamical changes on ozone. We contrast the sensitivity of the model system towards the representation of ozone with the changes associated with the removal of the interannual variability in SSTs. We show that the appearance of extreme events in the northern hemisphere winter stratosphere as modelled with the Unified Model is linked more to the representation of SSTs than it is to ozone. Copyright © 2004 Royal Meteorological Society
Agradient velocity, vortical motion and gravity waves in a rotating shallow‐water model
Authors: Sutyrin Georgi G. 
Published: September 2004

AbstractA new approach to modelling slow vortical motion and fast inertia‐gravity waves is suggested within the rotating shallow‐water primitive equations with arbitrary topography. The velocity is exactly expressed as a sum of the gradient wind, described by the Bernoulli function, B, and the remaining agradient part, proportional to the velocity tendency. Then the equation for inverse potential vorticity, Q, as well as momentum equations for agradient velocity include the same source of intrinsic flow evolution expressed as a single term J(B, Q), where J is the Jacobian operator (for any steady state J(B,Q)=0). Two components of agradient velocity are responsible for the fast inertia‐gravity wave propagation similar to the traditionally used divergence and ageostrophic vorticity.This approach allows for the construction of balance relations for vortical dynamics and potential vorticity inversion schemes even for moderate Rossby and Froude numbers assuming the characteristic value of |J(B,Q)|=ε to be small. The components of agradient velocity are used as the fast variables slaved to potential vorticity that allows for diagnostic estimates of the velocity tendency, the direct potential vorticity inversion with the accuracy of ε2 and the corresponding potential vorticity‐conserving agradient velocity balance model (AVBM). The ultimate limitations of constructing the balance are revealed in the form of the ellipticity condition for balanced tendency of the Bernoulli function which incorporates both known criteria of the formal stability: the gradient wind modified by the characteristic vortical Rossby wave phase speed should be subcritical. The accuracy of the AVBM is illustrated by considering the linear normal modes and coastal Kelvin waves in the f‐plane channel with topography. Copyright © 2004 Royal Meteorological Society
Platelet-Activating Factor Acetylhydrolase Is Not Associated with Carotid Intima-Media Thickness in Hypercholesterolemic Sicilian Individuals
Authors: Campo Salvatore , Sardo Maria A , Bitto Alessandra , Bonaiuto Antonio , Trimarchi Giuseppe , Bonaiuto Michele , Castaldo Maria , Saitta Carlo , Cristadoro Simona , Saitta Antonino 
Published: September 2004

AbstractBackground: Atherosclerosis is a complex, chronic disease that usually arises from the converging action of several pathogenic processes, including hypertension, hyperlipidemia, obesity, and the accumulation of oxidized LDL. Platelet-activating factor acetylhydrolase (PAF-AH) is a LDL- and HDL-bound enzyme that hydrolyzes and inactivates PAF and prevents LDL-cholesterol oxidation, thus delaying the onset of atherosclerotic disease.Methods: We evaluated the relationship between variants of the PAF-AH gene polymorphisms Arg92His, Ile198Thr, and Ala379Val and the presence of carotid atherosclerosis in 190 hypercholesterolemic Sicilian individuals. Carotid artery intima-media wall thickness (IMT) was measured as an indicator of early atherosclerotic disease. The participants were classified according to having normal (≤1 mm) or abnormal (≥1 mm) IMT and were also investigated for physical characteristics and biochemical indices, including PAF-AH activity.Results: PAF-AH activity and LDL concentrations were significantly correlated in hypercholesterolemic patients, but plasma PAF-AH activity and HDL were not significantly correlated in either IMT group. No significant differences were detected among the PAF-AH gene polymorphisms in both groups after correction for age, sex, body mass index, plasma glucose and lipid concentrations, PAF-AH activity, blood pressure, and smoking habits. The analysis of PAF-AH genotype distribution showed no significant differences in percentage of 92, 198, and 379 genotypes in both IMT groups.Conclusion: Our data provided no evidence that PAF-AH polymorphisms influence PAF-AH activity and atherosclerosis in hypercholesterolemic Sicilian patients.
Use of Animal Proteins to Limit Leaching of Active Copper Ions Preservatives from Treated Wood
Authors: Mazela B. , Polus-Ratajczak I. 
Published: September 2004

Summary
The concept of animal protein utilization aiming to reduce leaching of treatment salts from wood
was tested and verified. Animal proteins in the form of spray-dried animal blood plasma were used
as an addition to the water solution of fungicidal salt or included in the solution for soaking pre-treated
wood. The wood was subjected to thermal treatment which caused protein denaturation, a
process which changes the proteins' spatial conformation and reduces their solubility in water.
Scots pine wood (Pinus sylvestris L.) was treated with a water solution of copper sulfate using vacuum,
vacuum-soaking and vacuum-pressure methods. The animal proteins were added to the
treatment solutions or applied by soaking to samples pre-treated with the salt. After treatment, the
samples were heated to 100°C. After suitable conditioning, the wood was subjected to leaching.
The content of Cu2+ in the water extracts was determined by Atomic Absorption Spectrophotometry
(AAS).
Mode I Fracture Behaviour on the Growth Ring Scale and Cellular Level of Spruce (Picea abies [L.] Karst.) and Beech (Fagus sylvatica L.) Loaded in the TR Crack Propagation System
Authors: Frühmann K. , Burgert I. , Stanzl-Tschegg S. E. , Tschegg E. K. 
Published: September 2004

Summary
Crack propagation in wood is strongly influenced by the microscopic structure of the material. The
relationship between structure and function with regard to damage and fracture behaviour can
only be understood with a sufficiently fine level of examination. An experimental approach to perform
micro-wedge splitting tests on spruce and beech inside the chamber of an Environmental
Scanning Electron Microscope and under atmospheric conditions is presented. The specimens are
loaded in mode I in the TR crack propagation system. Based on the load-displacement diagram,
the characteristic parameters of fracture energy, critical load and initial elasticity are determined.
The load and displacement data for the in situ experiments are related to the obtained ESEM images
and allow a discussion of the fracture process on the cellular level. Density was found to be an
important factor for fracture mode and several crack arresting phenomena depending on the variation
of elasticity could be identified.
Mapping Radial,Tangential and Longitudinal Shrinkages and Relation to Tension Wood in Discs of the Tropical Tree Symphonia globulifera
Authors: Clair B. , Jaouen G. , Beauchêne J. , Fournier M. 
Published: September 2004

Summary
A method for measuring shrinkage resulting from drying in the three anisotropic directions is developed
and tested. Measurements are performed on sawn discs, a technique which simplifies
preparation and enables large numbers of measurements. Shrinkage values can be represented as
a map of the disc surface. The results indicate that comparisons between shrinkage distribution
and tension wood distribution on the discs show a clear relationship and can be measured with relatively
high accuracy in reference to the “shrinkage map”. In the long term, this method could be
useful in the timber industry as a means for choosing the direction in which logs are cut depending
on their type of wood composition.