bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of the Kinase Inhibitor SU11248 against Gastrointestinal Stromal Tumor Mutants Refractory to Imatinib Mesylate
Authors: Prenen Hans , Cools Jan , Mentens Nicole , Folens Cedric , Sciot Raf , Schöffski Patrick , Van Oosterom Allan , Marynen Peter , Debiec-Rychter Maria 
Published: April 2006

Abstract
Purpose: The majority of gastrointestinal stromal tumors harbor mutations in the receptor tyrosine kinases KIT or platelet-derived growth factor receptor A (PDGFRA), and respond to treatment with the tyrosine kinase inhibitor imatinib. Some tumors, however, show primary resistance to imatinib treatment, and most others become resistant during treatment. The most common mechanism of imatinib resistance involves specific mutations in the kinase domains of KIT or PDGFRA. We tested the activity of SU11248, an orally active small-molecule tyrosine kinase inhibitor, to inhibit important imatinib-resistant KIT and PDGFRA mutants.
Experimental Design: Primary imatinib-resistant tumor cells and cell lines expressing clinically identified imatinib-resistant KIT-V654A, KIT-T670I, or PDGFRA-D842V mutant isoforms were evaluated for sensitivity to SU11248 by Western immunoblotting and proliferation assays. Three patients with the KIT-V654A mutation were treated with SU11248.
Results: Based on ex vivo assays, SU11248 potently inhibits KIT kinase activity of V654A and T670I mutants and suppresses proliferation of the cells expressing these mutations. Sensitivity of KIT-V654A and KIT-T670I mutants to SU11248 was confirmed using cell lines expressing these mutants. In contrast, SU11248 did not potently inhibit the PDGFRA-D842V mutant. In agreement with these results, two of the three imatinib-resistant patients with the KIT-V654A mutation responded to SU11248 treatment.
Conclusions: These studies suggest that SU11248 may be a useful therapeutic agent to treat gastrointestinal stromal tumors harboring the imatinib-resistant KIT-V654A or KIT-T670I mutations, but it has no effect on the activity of the PDGFRA-D842V mutant. Specific kinase inhibitors should be designed to inhibit the constitutive activating PDGFRA mutation at codon 842.
High-Resolution Mapping of Tumor Redox Status by Magnetic Resonance Imaging Using Nitroxides as Redox-Sensitive Contrast Agents
Authors: Matsumoto Ken-ichiro , Hyodo Fuminori , Matsumoto Atsuko , Koretsky Alan P. , Sowers Anastasia L. , Mitchell James B. , Krishna Murali C. 
Published: April 2006

Abstract
Purpose: There is considerable research directed toward the identification and development of functional contrast agents for medical imaging that superimpose tissue biochemical/molecular information with anatomical structures. Nitroxide radicals were identified as in vivo radioprotectors. Being paramagnetic, they can provide image contrast in magnetic resonance imaging (MRI) and electron paramagnetic resonance imaging (EPRI). The present study sought to determine the efficacy of nitroxide radioprotectors as functional image contrast agents.
Experimental Design: Nitroxide radioprotectors, which act as contrast agents, were tested by EPRI and MRI to provide tissue redox status information noninvasively.
Results: Phantom studies showed that the nitroxide, 3-carbamoyl-PROXYL (3CP), undergoes time-dependent reduction to the corresponding diamagnetic hydroxylamine only in the presence of reducing agents. The reduction rates of 3CP obtained by EPRI and MRI were in agreement suggesting the feasibility of using MRI to monitor nitroxide levels in tissues. The levels of 3CP were examined by EPRI and MRI for differences in reduction between muscle and tumor (squamous cell carcinoma) implanted in the hind leg of C3H mice simultaneously. In vivo experiments showed a T1-dependent image intensity enhancement afforded by 3CP which decreased in a time-dependent manner. Reduction of 3CP was found to be the dominant mechanism of contrast loss. The tumor regions exhibited a faster decay rate of the nitroxide compared to muscle (0.097 min-1 versus 0.067 min-1, respectively).
Conclusions: This study shows that MRI can be successfully used to co-register tissue redox status along with anatomic images, thus providing potentially valuable biochemical information from the region of interest.
Spatial Forecasts of Maximum Hail Size Using Prognostic Model Soundings and HAILCAST
Authors: Brimelow Julian C. , Reuter Gerhard W. , Goodson Ron , Krauss Terrence W. 
Published: April 2006

Abstract
Forecasting the occurrence of hail and the maximum hail size is a challenging problem. This paper investigates the feasibility of producing maps of the forecast maximum hail size over the Canadian prairies using 12-h prognostic soundings from an operational NWP model as input for a numerical hail growth model. Specifically, the Global Environmental Multiscale model run by the Canadian Meteorological Center is used to provide the initial data for the HAILCAST model on a 0.5° × 0.5° grid. Maps depicting maximum hail size for the Canadian prairies are generated for 0000 UTC for each day from 1 June to 31 August 2000. The forecast hail-size maps are compared with radar-derived vertically integrated liquid data over southern Alberta and surface hail reports. Verification statistics suggest that the forecast technique is skillful at identifying the occurrence of a hail day versus no-hail day up to 12 h in advance. The technique is also skillful at predicting the main threat areas. The maximum diameter of the hailstones is generally forecast quite accurately when compared with surface observations. However, the technique displays limited skill when forecasting the distribution of hail on a small spatial scale.
Tibiofemoral Contact Mechanics after Serial Medial Meniscectomies in the Human Cadaveric Knee
Authors: Lee Stephen J. , Aadalen Kirk J. , Malaviya Prasanna , Lorenz Eric P. , Hayden Jennifer K. , Farr Jack , Kang Richard W. , Cole Brian J. 
Published: April 2006

Background There is no consensus regarding the extent of meniscectomy leading to deleterious effects on tibiofemoral contact mechanics. Hypothesis The meniscus aids in optimizing tibiofemoral contact mechanics, increasing contact area, and decreasing contact stress. Study Design Controlled laboratory study. Methods Twelve fresh-frozen human cadaveric knees each underwent 15 separate testing conditions—5 serial 20-mm posterior medial meniscectomy conditions (intact, 50% radial width, 75% radial width, segmental, and total meniscectomy) at 3 flexion angles (0°, 30°, and 60°)—under an 1800-N axial load. Tekscan sensors were used to measure total force and medial force, contact area, mean contact stress, and peak contact stress. Results All posterior medial meniscectomy conditions resulted in significantly decreased contact areas and increased mean and peak contact stresses compared with the intact state (P < .05). The changes in contact mechanics after segmental and total posterior medial meniscectomies were not statistically different (P > .05). Incremental changes in contact area and mean contact stress increased as more peripheral portions of the medial meniscus were removed, whereas peak contact stresses exhibited similar incremental changes throughout all meniscectomy conditions. Conclusions The meniscus is a crucial load-bearing structure, optimizing contact area and minimizing contact stress. Loss of hoop tension (ie, segmental meniscectomy) is equivalent to total meniscectomy in load-bearing terms. The peripheral portion of the medial meniscus provides a greater contribution to increasing contact areas and decreasing mean contact stresses than does the central portion, whereas peak contact stresses increase proportionally to the amount of meniscus removed. Clinical Relevance Because the degree of meniscectomy leading to clinically significant outcomes is unknown, a prudent strategy is to preserve the greatest amount of meniscus possible.
Meniscal Allograft Transplantation in the Sheep Knee
Authors: Kelly Bryan T. , Potter Hollis G. , Deng Xiang-Hua , Pearle Andrew D. , Turner A. Simon , Warren Russell F. , Rodeo Scott A. 
Published: April 2006

Background Early protection of articular cartilage, before degenerative changes appear on radiographs, should result in better long-term results, but scientific evidence regarding the effectiveness of meniscal transplantation is lacking. Purpose To assess the chondroprotective effects of a new meniscal allograft transplantation animal model and evaluate a magnetic resonance imaging parameter, T2 mapping, in articular cartilage after meniscectomy and meniscal transplantation. Study Design Controlled laboratory study. Methods Forty-five skeletally mature sheep were placed into 3 surgical groups lateral meniscectomy (n = 24), meniscal allograft transplant (n = 17), and sham (n = 4). Animals were sacrificed at 2, 4, or 12 months. Cartilage was assessed by gross inspection, magnetic resonance imaging, T2 mapping, biomechanical testing, and semiquantitative histologic analysis. Results There were no differences between the sham operation and nonoperated control limbs. Compared with control limbs, meniscectomy resulted in significant increases in cartilage degeneration by all objective criteria (P < .01). Compared with meniscectomy, meniscal allograft transplantation resulted in significant decreases in cartilage degeneration (P < .02). There were significant correlations between T2-mapping data and all other traditional outcomes measures (P < .05, r2 = 0.37-0.67). Compared with the nonoperated control limbs, allograft transplants demonstrated no significant differences at 2 months in any category, except magnetic resonance imaging data. By 4 months, nonoperated control limbs demonstrated significantly less wear compared to allograft limbs in all categories except modified Mankin scores. Conclusion This model demonstrated significant chondroprotection compared with meniscectomy but demonstrated more cartilage wear at 4 months compared to control limbs. A high degree of allograft cell viability and vascular ingrowth was seen in allograft explants. T2 mapping may provide an accurate noninvasive measure of early cartilage degeneration after meniscectomy, as well as cartilage protection after meniscal allograft transplantation. Clinical Relevance This study establishes a reliable animal model for meniscal allograft transplantation and provides evidence for the utility of T2 mapping at clinically relevant magnetic resonance imaging field strengths for evaluation of early cartilage degeneration.
Improving health care quality for racial/ethnic minorities: a systematic review of the best evidence regarding provider and organization interventions
Authors: Beach Mary Catherine , Gary Tiffany L , Price Eboni G , Robinson Karen , Gozu Aysegul , Palacio Ana , Smarth Carole , Jenckes Mollie , Feuerstein Carolyn , Bass Eric B , Powe Neil R , Cooper Lisa A 
Published: April 2006

Abstract

Background
Despite awareness of inequities in health care quality, little is known about strategies that could improve the quality of healthcare for ethnic minority populations. We conducted a systematic literature review and analysis to synthesize the findings of controlled studies evaluating interventions targeted at health care providers to improve health care quality or reduce disparities in care for racial/ethnic minorities.

Methods
We performed electronic and hand searches from 1980 through June 2003 to identify randomized controlled trials or concurrent controlled trials. Reviewers abstracted data from studies to determine study characteristics, results, and quality. We graded the strength of the evidence as excellent, good, fair or poor using predetermined criteria. The main outcome measures were evidence of effectiveness and cost of strategies to improve health care quality or reduce disparities in care for racial/ethnic minorities.

Results
Twenty-seven studies met criteria for review. Almost all (n = 26) took place in the primary care setting, and most (n = 19) focused on improving provision of preventive services. Only two studies were designed specifically to meet the needs of racial/ethnic minority patients. All 10 studies that used a provider reminder system for provision of standardized services (mostly preventive) reported favorable outcomes. The following quality improvement strategies demonstrated favorable results but were used in a small number of studies: bypassing the physician to offer preventive services directly to patients (2 of 2 studies favorable), provider education alone (2 of 2 studies favorable), use of a structured questionnaire to assess adolescent health behaviors (1 of 1 study favorable), and use of remote simultaneous translation (1 of 1 study favorable). Interventions employing more than one main strategy were used in 9 studies with inconsistent results. There were limited data on the costs of these strategies, as only one study reported cost data.

Conclusion
There are several promising strategies that may improve health care quality for racial/ethnic minorities, but a lack of studies specifically targeting disease areas and processes of care for which disparities have been previously documented. Further research and funding is needed to evaluate strategies designed to reduce disparities in health care quality for racial/ethnic minorities.
Association of PTPN22 1858 single-nucleotide polymorphism with rheumatoid arthritis in a German cohort: higher frequency of the risk allele in male compared to female patients
Authors: Pierer Matthias , Kaltenhäuser Sylke , Arnold Sybille , Wahle Matthias , Baerwald Christoph , Häntzschel Holm , Wagner Ulf 
Published: April 2006

AbstractThe functional single-nucleotide polymorphism (SNP) of the gene PTPN22 is a susceptibility locus for rheumatoid arthritis (RA). The study presented here describes the association of the PTPN22 1858T allele with RA in a German patient cohort; 390 patients with RA and 349 controls were enrolled in the study. For 123 patients, clinical and radiographic documentation over 6 years was available from the onset of disease. Genotyping of the PTPN22 1858 SNP was performed using an restriction fragment length polymorphism PCR-based genotyping assay. The odds ratio to develop RA was 2.57 for carriers of the PTPN22 1858T allele (95% confidence interval (CI) 1.85–3.58, p < 0.001), and 5.58 for homozygotes (95% CI 1.85–16.79). The PTPN22 1858T allele was significantly associated not only with rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) positive RA, but also with RF and anti-CCP negative disease. The frequency of the PTPN22 1858T allele was increased disproportionately in male patients (53.8% compared to 33.0% in female patients, p < 0.001), and the resulting odds ratio for male carriers was increased to 4.47 (95% CI 2.5–8.0, p < 0.001). Moreover, within the male patient population, the rare allele was significantly associated with the HLA-DRB1 shared epitope (p = 0.01). No significant differences in disease activity or Larsen scores were detected. The results provide further evidence that the PTPN22 1858T allele is associated with RA irrespective of autoantibody production. The increased frequency of the risk allele in male patients and its association with the shared epitope indicate that the genetic contribution to disease pathogenesis might be more prominent in men.
Traumatic spinal cord injury: the relationship between pathology and clinical implications
Authors: El Masri(y) WS 
Published: April 2006

The pathological effects of traumatic spinal cord injuries (SCI) encompass the pathology affecting the spinal cord. As a result of the interruption of spinal cord conduction, one or more pathological and patho-physiological processes affect almost every system of the human body. Knowledge of the pathological processes that affect the spinal cord and the various systems of the body is essential for the safe and good management of these patients. The small incidence (10-15 per million per year) of these highly complex conditions makes it difficult for skills and experience to develop in District General Hospitals in the management of these patients. The associated sensory impairment or loss present diagnostic challenges to the clinician in almost every aspect of paralysis and throughout the patient’s life. In the acute stage simultaneous good management of the multi-system impairments and malfunctions giving equal attention to all systems including that of the traumatized spine is the key to good quality outcome. Concentrating resources at any one time on any one particular aspect of paralysis is unlikely to yield a similarly good outcome. The neurological outcome does not depend only on the quality of the management of the SCI. The traumatized physiologically unstable spinal cord is vulnerable and unable to protect itself from non-mechanical complications outside the spinal canal, many of which can easily develop in patients with SCI adding to the threats from the biomechanical instability. To date there are many controversies in the management of many aspects of paralysis at all stages following injury. One of the main current controversies is in the management of the SCI itself. There are many reasons that seem to perpetuate this controversy. Some of the reasons may be related to different interpretations of the pathological processes that affect the vertebral axis and the spinal cord as well as their effects on neurological outcome. The natural history of neurological recovery following SCI is not always duly acknowledged.
Forkhead Box Protein P1 Expression in Mucosa-Associated Lymphoid Tissue Lymphomas Predicts Poor Prognosis and Transformation to Diffuse Large B-Cell Lymphoma
Authors: Sagaert Xavier , de Paepe Pascale , Libbrecht Louis , Vanhentenrijk Vera , Verhoef Gregor , Thomas Jose , Wlodarska Iwona , De Wolf-Peeters Christiane 
Published: April 2006

PurposeGene expression profiling studies have reported upregulated mRNA expression of forkhead box protein P1 (FOXP1) in response to normal B-cell activation and high expression in a poor prognosis subtype of diffuse large B-cell lymphoma (DLBCL). Recently, it was also found that FOXP1 rearrangements and expression of its protein occur in mucosa-associated lymphoid tissue (MALT) lymphomas. In this study, we investigated FOXP1 expression in its relationship to morphology, genetic features, and prognosis in a series of 70 MALT lymphomas.Patients and MethodsAll samples were morphologically reviewed and stained for FOXP1. Presence of structural and/or numeric aberrations of the FOXP1, BCL10, and MALT1 genes was investigated. For all patients, a complete clinical data set was collected.ResultsWe detected nuclear expression of FOXP1 in 20 of the 70 MALT lymphomas (nine of them featuring structural or numeric aberrations of the FOXP1 locus). FOXP1 positivity was confined to MALT lymphomas with poor clinical outcome (with impact of FOXP1 expression on relapse rate and disease-free survival). It was also found that MALT lymphomas with strong FOXP1 expression are at risk of transforming into an aggressive DLBCL of nongerminal center phenotype if they feature, in addition, a polymorphic histology and the presence of trisomy 3 and 18.ConclusionThe data presented show that FOXP1 expression is an independent prognostic factor in MALT lymphomas. The data also support the hypothesis that a subgroup of nongerminal center DLBCLs (those marked by FOXP1 expression and trisomy 3 and 18) might represent a large-cell variant of MALT lymphomas.
Enantioselective Catalysis Performed by Bilayer-type Artificial Aminotransferase. Effect of a Chiral Binaphthol Moiety Placed in the Reaction Site
Authors: Kikuchi Jun-ichi , Zhang Zhi-Yi , Miyajima Tetsuya , Murakami Yukito 
Published: April 2006

Abstract
A supramolecular bilayer assembly, composed of a cationic peptide lipid having an (S)-alanine residue, an additional one having an (S)-binaphthol moiety, a hydrophobic pyridoxamine derivative, and copper(II) ions, performed substrate-selective catalysis as a vitamin B6-dependent artificial aminotransferase to transform α-keto acids into the corresponding α-amino acids in an enantiomeric excess of the d-isomer.
An Aminimide as an Extractant for Heavy- and Transition Metal Cations
Authors: Inokuma Seiichi , Hasegawa Kaori , Sakai Shigefumi , Nishimura Jun 
Published: April 2006

Abstract
The compounds possessing two aminimide groups directly attached to each other showed moderate affinity toward heavy- and transition metal cations on the liquid-liquid extraction. It is thought that this takes the five membered ring chelation which results in high lipophilic complexations to extract the cations into the organic phase.
Flow-Through-Measurements for Glucose Detection Using All-Solid-State Electrochemical Cells
Authors: Lisdat Fred , Miura Norio , Yamazoe Noboru 
Published: April 2006

Abstract
A potentiometric glucose sensor applicable for flow-trough-measurements was developed. The sensor can be represented by the following electrochemical scheme: Reference layer (Ag/AgCl) / NASICON / Pt, enzyme layer (GOD). The response to glucose was found to be reversible with a 90% response time of 50–90 s and a sensitivity of −55 ± 2 mV/dec. The stability of the internal reference contact as well as the reproducibility of the sensor signal were investigated. The compact sensor design allows easy replacement of the sensor within a flow-through-system.
Potentiometric Sensor Using Stabilized Zirconia and Tungsten Oxide for Hydrogen Sulfide
Authors: Yan Yongtie , Miura Norio , Yamazoe Noboru 
Published: April 2006

Abstract
A solid-state electrochemical device based on Y2O3-stabilized zirconia was found to respond well to 0.6–12 ppm H2S in air at 400 °C, when its surface exposed to H2S was coated with a layer of WO3. EMF decreased with an increase in H2S concentration at a rate of −40 mV/decade. It is proposed that in this device WO3 acts as a semiconductor electrode, its mixed potential being determined by the electrode reactions taking place at the zirconia/WO3 interface.
Convenient Synthesis of Bis-1,3-dithiolium Salts by One-electron Oxidation of Tetrathiafulvalene with Oxoaminium Salts
Authors: Yoshida Eri , Takata Toshikazu , Endo Takeshi , Ishizone Takashi , Hirao Akira , Nakahama Seiichi 
Published: April 2006

Abstract
Several bis-1,3-dithiolium salts, radical cation salts of tetrathiafulvalene were synthesized in quantitative yields by oxidation of tetrathiafulvalene with oxoaminium salts for 1min at room temperature.
A New Parameter for Maturity Assessment of Organic Materials in Sediments Based on Thermal Isomerization of Monomethylphenanthrenes
Authors: Shimoyama Akira , Nakano Yoshinobu , Nomoto Shinya 
Published: April 2006

Abstract
Monomethylphenanthrenes(MPs) were isomerized by heating in the presence of Na-montmorillonite to give a mixture of four isomers (1-, 2-, 3-, and 9-MP). The ratio of 1- and 2-MP produced from each isomer reached a constant value after appropriate time of heating. This ratio provides a new parameter for maturity assessment of sedimentary organic materials.
Incorporation of CO and NO Ligands in the Reaction of Benzyl Bromides with Tetrabutylammonium Tricarbonylnitrosylferrate
Authors: Nakanishi Saburo , Shimizu Yasuyo 
Published: April 2006

Abstract
Reaction of benzyl bromides with tetrabutylammonium tricarbonylnitrosylferrate afforded N-benzylphenylacetamides via incorporation of CO and NO ligands accompanied with dibenzyl ketones. A noticeable substituent effect on the amide-forming reaction was observed.
Detection of Hydroxyl Radical from Photoexcited Chlorophylls on Magnesium Oxide Powder in Aqueous Media Using the ESR Spin Trapping Technique
Authors: Noda Hiroyuki , Oikawa Kazuo , Ohya-Nishiguchi Hiroaki , Kamada Hitoshi 
Published: April 2006

Abstract
A potent active oxygen of hydroxyl radical has been detected in aqueous media of the photoexcited chlorophylls on MgO powder by using the ESR spin trapping technique. The mechanism for the production of the radical is discussed refering to three-electrons reduction of oxygen by the photoexcited chlorophylls on MgO.