bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative proteomic analysis of all-trans-retinoic acid treatment reveals systematic posttranscriptional control mechanisms in acute promyelocytic leukemia
Authors: Harris Michael N. , Ozpolat Bulent , Abdi Fadi , Gu Sheng , Legler Allison , Mawuenyega Kwasi G. , Tirado-Gomez Maribel , Lopez-Berestein Gabriel , Chen Xian 
Published: May 2004

AbstractAll-trans-retinoic acid (ATRA) induces growth inhibition, differentiation, and apoptosis in cancer cells, including acute promyelocytic leukemia (APL). In APL, expression of promyelocytic leukemia protein retinoic acid receptor–α (PML-RARα) fusion protein, owing to the t(15; 17) reciprocal translocation, leads to a block in the promyelocytic stage of differentiation. Here, we studied molecular mechanisms involved in ATRA-induced growth inhibition and myeloid cell differentiation in APL. By employing comprehensive high-throughput proteomic methods of 2-dimensional (2-D) gel electrophoresis and amino acid–coded mass tagging coupled with electrospray ionization (ESI) mass spectrometry, we systematically identified a total of 59 differentially expressed proteins that were consistently modulated in response to ATRA treatment. The data revealed significant down-regulation of eukaryotic initiation and elongation factors, initiation factor 2 (IF2), eukaryotic initiation factor 4AI (eIF4AI), eIF4G, eIF5, eIF6, eukaryotic elongation factor 1A-1 (eEF1A-1), EF-1-δ, eEF1γ, 14-3-3ϵ, and 14-3-3ζ/δ (P &lt; .05). The translational inhibitor DAP5/p97/NAT1 (death-associated protein 5) and PML isoform-1 were found to be up-regulated (P &lt; .05). Additionally, the down-regulation of heterogeneous nuclear ribonucleoproteins (hnRNPs) C1/C2, UP2, K, and F; small nuclear RNPs (snRNPs) D3 and E; nucleoprotein tumor potentiating region (TPR); and protein phosphatase 2A (PP2A) were found (P &lt; .05); these were found to function in pre-mRNA processing, splicing, and export events. Importantly, these proteomic findings were validated by Western blot analysis. Our data in comparison with previous cDNA microarray studies and our reverse transcription–polymerase chain reaction (RT-PCR) experiments demonstrate that broad networks of posttranscriptional suppressive pathways are activated during ATRA-induced growth inhibition processes in APL.
Identification of a novel mutation (C321X) in HJV
Authors: Huang Franklin W. , Rubio-Aliaga Isabel , Kushner James P. , Andrews Nancy C. , Fleming Mark D. 
Published: May 2004

Abstract
Juvenile hemochromatosis is a rare autosomal recessive disorder characterized by the early onset of severe iron overload. We report the occurrence of compound heterozygous mutations in hemojuvelin (HJV), including a termination codon, in a patient with juvenile hemochromatosis but no family history of iron disorders. (Blood. 2004;104:2176-2177)
Recessively inherited coagulation disorders
Authors: Mannucci Pier Mannuccio , Duga Stefano , Peyvandi Flora 
Published: May 2004

AbstractDeficiencies of coagulation factors other than factor VIII and factor IX that cause bleeding disorders are inherited as autosomal recessive traits and are rare, with prevalences in the general population varying between 1 in 500 000 and 1 in 2 million for the homozygous forms. As a consequence of the rarity of these deficiencies, the type and severity of bleeding symptoms, the underlying molecular defects, and the actual management of bleeding episodes are not as well established as for hemophilia A and B. We investigated more than 1000 patients with recessively inherited coagulation disorders from Italy and Iran, a country with a high rate of recessive diseases due to the custom of consanguineous marriages. Based upon this experience, this article reviews the genetic basis, prevalent clinical manifestations, and management of these disorders. The steps and actions necessary to improve the condition of these often neglected patients are outlined.
Effect of up-front daclizumab when combined with steroids for the treatment of acute graft-versus-host disease: results of a randomized trial
Authors: Lee Stephanie J. , Zahrieh David , Agura Edward , MacMillan Margaret L. , Maziarz Richard T. , McCarthy Philip L. , Ho Vincent T. , Cutler Corey , Alyea Edwin P. , Antin Joseph H. , Soiffer Robert J. 
Published: May 2004

AbstractThe standard initial therapy for acute graft-versus-host disease (GVHD) is corticosteroids. Daclizumab is a humanized monoclonal antibody against the interleukin 2 (IL-2) receptor expressed on activated T lymphocytes. Because of daclizumab's favorable toxicity profile and response rate in steroid-resistant GVHD, a multicenter, double-blinded, randomized study of corticosteroids with or without daclizumab for initial treatment of acute GVHD was conducted. A total of 102 evaluable subjects of the targeted 166 were enrolled at 5 participating sites. Methylprednisolone at a dose of 2 mg/kg or daily equivalent was given in conjunction with daclizumab 1 mg/kg or placebo on study days 1, 4, 8, and weekly as long as clinically indicated. The groups were balanced for clinical characteristics. GVHD response rates by study day 42 were similar (53% vs 51%; P = .85). The study was halted after a planned interim analysis showed a significantly worse 100-day survival in the group receiving corticosteroids plus daclizumab (77% vs 94%; P = .02). Overall survival at 1 year was also inferior in the combination arm (29% vs 60%; P = .002). Both relapse- and GVHD-related mortality contributed to the increased mortality in the combination group. The combination of corticosteroids and daclizumab should not be used as initial therapy of acute GVHD.
Endogenous angiotensin II in the regulation of hypoxic pulmonary vasoconstriction in anaesthetized dogs
Authors: Hubloue Ives , Rondelet Benoît , Kerbaul François , Biarent Dominique , Milani Guiti Malekzadeh , Staroukine Michel , Bergmann Pierre , Naeije Robert , Leeman Marc 
Published: May 2004

Abstract
Introduction
The role played by several vasoactive mediators that are synthesized and released by the pulmonary vascular endothelium in the regulation of hypoxic pulmonary vasoconstriction (HPV) remains unclear. As a potent vasoconstrictor, angiotensin II could be involved. We tested the hypothesis that angiotensin-converting enzyme inhibition by enalaprilat and type 1 angiotensin II receptor blockade by candesartan would inhibit HPV.

Methods
HPV was evaluated in anaesthetized dogs, with an intact pulmonary circulation, by examining the increase in the Ppa–Ppao gradient (mean pulmonary artery pressure minus occluded pulmonary artery pressure) that occurred in response to hypoxia (inspiratory oxygen fraction of 0.1) at constant pulmonary blood flow. Plasma renin activity and angiotensin II immunoreactivity were measured to determine whether activation or inhibition of the renin–angiotensin system was present.

Results
Administration of enalaprilat and candesartan did not affect the Ppa–Ppao gradient at baseline or during hypoxia. Plasma renin activity and angiotensin II immunoreactivity increased during hypoxia, and subsequent measurements were consistent with effective angiotensin-converting enzyme inhibition after administration of enalaprilat, and with angiotensin receptor blockade after administration of candesartan.

Conclusion
These results suggest that, although the renin–angiotensin system was activated in hypoxia, angiotensin II is not normally involved in mediating acute HPV.
The Effects of Estrogen on the Expression of Genes Underlying the Differentiation of Somatic Cells in the Murine Gonad
Authors: Britt Kara L. , Stanton Peter G. , Misso Marie , Simpson Evan R. , Findlay Jock K. 
Published: May 2004

AbstractEstrogen (17β-estradiol, E2)-deficient aromatase knockout (ArKO) mice develop Sertoli and Leydig cells at puberty. We hypothesized that estrogen, directly or indirectly, regulates genes responsible for somatic cell differentiation and steroidogenesis. ArKO ovaries expressed estrogen receptors α and β, and LH receptor, indices of estrogen responsiveness in the ovary. Wild-type (Wt) and ArKO mice received either E2 or placebo for 3 wk, from 7–10 wk of age. E2 decreased serum FSH and LH and increased uterine weights of 10-wk-old ArKO mice. We measured mRNA expression of Sertoli cell, Sry-like HMG box protein 9 (Sox9); three upstream transcription factors, liver receptor homolog-1 (Lrh-1), steroidogenic factor 1, and dosage-sensitive sex reversal adrenal hypoplasia congenital critical region on the X chromosome gene 1; and one downstream factor, Müllerian-inhibiting substance. Placebo-treated ArKO ovaries have increased Sox9 (15-fold; P &lt; 0.001), Müllerian-inhibiting substance (2.9-fold), Lrh-1 (7.7-fold), and dosage-sensitive sex reversal adrenal hypoplasia congenital critical region on the X chromosome gene 1 (12-fold) expression compared with Wt at 10 wk. Steroidogenic factor 1 was similar to Wt. Consistent with increased serum T levels and Leydig cells in their ovaries, placebo-treated ArKO ovaries had increased 17α-hydroxylase, 17β-hydroxysteroid dehydrogenase type-3, and 17β-hydroxysteroid dehydrogenase type-1 expression compared with Wt at 10 wk. E2 treatment for 3 wk improved the ovarian phenotype, decreased development of Sertoli cells, decreased the expression of Sox9, Lrh-1, and the steroidogenic enzymes in ArKO ovaries, and induced ovulation in some cases. In conclusion, the expression of the genes regulating somatic cell differentiation is directly or indirectly responsive to estrogen.
Region-Specific Reduction in Leptin-Induced Phosphorylation of Signal Transducer and Activator of Transcription-3 (STAT3) in the Rat Hypothalamus Is Associated with Leptin Resistance during Pregnancy
Authors: Ladyman S. R. , Grattan D. R. 
Published: May 2004

Abstract
Leptin concentrations increase during pregnancy, but this does not prevent the pregnancy-induced increase in food intake, suggesting a state of leptin resistance. This study investigated the response to intracerebroventricular leptin administration in pregnant rats. After fasting, nonpregnant, d-7 and d-14 pregnant rats received leptin (4 μg) or vehicle, then food intake was measured. Serial blood samples were collected in another group of rats to determine plasma leptin concentrations. Further groups of d-14 pregnant and nonpregnant rats were killed after leptin or vehicle treatment, and brains were collected. Hypothalamic nuclei were microdissected, and levels of signal transducer and activator of transcription (STAT)3 phosphorylation were measured using Western blot analysis. Fasting decreased leptin concentrations in both pregnant and nonpregnant rats. Leptin treatment significantly reduced food intake in nonpregnant and d-7 pregnant rats but not in d-14 pregnant rats. In addition, there was no postfasting hyperphagic response in the pregnant rats. In the pregnant rats, leptin-induced STAT3 phosphorylation was suppressed in the arcuate nucleus and, to a lesser extent, in the ventromedial hypothalamus (VMH), compared with nonpregnant rats. Unstimulated STAT3 levels were also decreased in the VMH during pregnancy. Leptin-induced phosphorylation of STAT3 in the dorsomedial and lateral hypothalamus was not different between pregnant and nonpregnant rats. These data indicate that pregnant rats become resistant to the satiety action of leptin. Furthermore, leptin-induced activation of the STAT3 is impaired during pregnancy, specifically in the arcuate nucleus and VMH. These data support the hypothesis that pregnancy is a state of hypothalamic leptin resistance.
FTY720 and Cyclosporine: Evaluation for a Pharmacokinetic Interaction
Authors: Kovarik John M , Schmouder Robert L , Barilla Denise , Büche Monika , Rouilly Marisel , Berthier Stephane , Wang Yibin , Van Saders Claudia , Mayer Thomas , Gottlieb Alice B 
Published: May 2004

BACKGROUND: FTY720 is a sphingosine-1-phosphate receptor agonist intended for use in immunoprophylaxis regimens to prevent acute rejection after organ transplantation. OBJECTIVE: To evaluate the potential for a pharmacokinetic drug interaction between the immunomodulator FTY720 and cyclosporine to support the use of this drug combination in organ transplantation. METHODS: In this open-label, randomized crossover study, 12 subjects with psoriasis received a single dose of FTY720 1 mg alone and on day 5 of an 8-day course of cyclosporine 200 mg twice daily. The single-dose pharmacokinetics of FTY720 and the steady-state pharmacokinetics of cyclosporine were characterized when given alone and during coadministration. Routine safety data were collected, with special attention to total blood lymphocyte counts and heart rate. RESULTS: Cyclosporine coadministration compared with FTY720 given alone did not significantly alter FTY720 maximum concentration (Cmax) (0.57 ± 0.17 vs 0.58 ± 0.19 • ng/mL, respectively) or AUC0-t (41 ± 13 vs 41 ± 13 ng • h/mL, respectively). Likewise for cyclosporine, FTY720 coadministration did not alter the steady-state Cmax compared with cyclosporine given alone (1452 ± 308 vs 1376 ± 149 ng/mL, respectively) or AUCτ (6385 ± 1578 vs 6031 ± 1051 ng • h/mL, respectively). Mean lymphocyte counts decreased from baseline by an average of 35% over the first 2 days after FTY720 administration and thereafter increased to prestudy values by day 5 similarly in the absence and presence of cyclosporine. The morning mean supine heart rate decreased approximately 10% and returned to prestudy rates by day 5 after administration of FTY720 alone and with cyclosporine. Heart rate changes were asymptomatic in all study participants. One subject experienced asymptomatic second-degree type 1 atrioventricular (Wenckebach) block. CONCLUSIONS: The pharmacokinetics of single-dose FTY720 and steady-state cyclosporine were not altered during coadministration.
Natriuretic Peptides as Markers of Mild Forms of Left Ventricular Dysfunction: Effects of Assays on Diagnostic Performance of Markers
Authors: Hammerer-Lercher Angelika , Ludwig Wilma , Falkensammer Gerda , Müller Silvana , Neubauer Elke , Puschendorf Bernd , Pachinger Otmar , Mair Johannes 
Published: May 2004

Abstract
Background: We compared the performance of different natriuretic peptides to diagnose mild forms of left ventricular dysfunction (LVD) and investigated the influence of measuring B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) with different assays on the diagnostic performance of these markers.
Methods: We measured BNP (Triage® BNP), NT-proBNP (Biomedica), and N-terminal pro-A-type natriuretic peptide (NT-proANP; Biomedica) in 130 consecutive patients (age range, 28–83 years) with clinically suspected mild LVD. In patients with sufficient sample volume, we measured BNP and NT-proBNP with additional assays (Shionoria and Roche, respectively).
Results: For identifying patients with mild systolic LVD, BNP and NT-proBNP were the best markers, with mean (95% confidence interval) areas under the curves (AUC) of 0.78 (0.63–0.89) and 0.75 (0.58–0.87), respectively. However, the diagnostic performance of NT-proANP [AUC, 0.64 (0.48–0.77)] was significantly worse than that of BNP (P = 0.014). Both BNP assays (Triage and Shionoria) and both NT-proBNP assays (Biomedica and Roche) performed equally well for the diagnosis of systolic LVD despite the poor agreement between NT-proBNP assays. In patients with isolated diastolic LVD, the diagnostic performance of the Triage BNP [AUC, 0.70 (0.56–0.81)] was significantly better (P = 0.006) than that of Biomedica NT-proBNP [0.49 (0.34–0.65)]. Furthermore, the performance of the Biomedica NT-proBNP assay was significantly worse (P = 0.03) than that of the Roche NT-proBNP assay for diagnosis of isolated diastolic LVD.
Conclusions: The performance of BNP for the diagnosis of systolic or diastolic LVD is not affected by the assay used, whereas the performance of NT-proBNP for the diagnosis of isolated diastolic LVD is assay dependent.
ROC Curves in Clinical Chemistry: Uses, Misuses, and Possible Solutions
Authors: Obuchowski Nancy A , Lieber Michael L , Wians Frank H 
Published: May 2004

Abstract
Background: ROC curves have become the standard for describing and comparing the accuracy of diagnostic tests. Not surprisingly, ROC curves are used often by clinical chemists. Our aims were to observe how the accuracy of clinical laboratory diagnostic tests is assessed, compared, and reported in the literature; to identify common problems with the use of ROC curves; and to offer some possible solutions.
Methods: We reviewed every original work using ROC curves and published in Clinical Chemistry in 2001 or 2002. For each article we recorded phase of the research, prospective or retrospective design, sample size, presence/absence of confidence intervals (CIs), nature of the statistical analysis, and major analysis problems.
Results: Of 58 articles, 31% were phase I (exploratory), 50% were phase II (challenge), and 19% were phase III (advanced) studies. The studies increased in sample size from phase I to III and showed a progression in the use of prospective designs. Most phase I studies were powered to assess diagnostic tests with ROC areas ≥0.70. Thirty-eight percent of studies failed to include CIs for diagnostic test accuracy or the CIs were constructed inappropriately. Thirty-three percent of studies provided insufficient analysis for comparing diagnostic tests. Other problems included dichotomization of the gold standard scale and inappropriate analysis of the equivalence of two diagnostic tests.
Conclusion: We identify available software and make some suggestions for sample size determination, testing for equivalence in diagnostic accuracy, and alternatives to a dichotomous classification of a continuous-scale gold standard. More methodologic research is needed in areas specific to clinical chemistry.
HyperScout: Linkvorschau im World Wide Web (HyperScout: Link Preview for the World Wide Web)
Authors: Weinreich Harald , Obendorf Hartmut , Lamersdorf Winfried 
Published: May 2004

Zusammenfassung
Die Benutzung eines Web-Browsers ist einfach zu erlernen, dennoch stellt die Navigation im Web selbst für erfahrene Benutzer immer wieder Herausforderungen bereit. Einer der Gründe dafür liegt in der Vielfalt von Linkarten und Linkzielen, die für den Benutzer oft nicht transparent sind und ihn so vor Überraschungen stellen, nachdem er einen Link angeklickt hat. Das Projekt HyperScout beschäftigt sich mit Möglichkeiten, die Navigation im Web zu vereinfachen, indem man Informationen zum Typ des Links und zum referenzierten Objekt für den Benutzer sichtbar macht. Dieser Bericht stellt die entwickelten Konzepte und die Ergebnisse einer Evaluation des daraus abgeleiteten Prototyps vor. Die Ergebnisse geben Aufschlüsse darüber, welche Informationen Benutzern vor der Anwahl eines Links hilfreich sind und wie sie dargestellt werden könnten.
THE ASIA-EUROPE MEETING AND INTER-REGIONALISM: Toward a Theory of Multilateral Utility
Authors: Dent Christopher M. 
Published: May 2004

Abstract
The Asia-Europe Meeting framework was created in 1996, its primary purpose being to fortify relations between the East Asian region and the European Union. Moreover, ASEM partners must not only concern themselves with developing closer interregional ties but also attend to the significant global impact of their partnership, and thus the responsibilities that lie therein.
LEADERSHIP TRANSITION, INTRA-PARTY DEMOCRACY, AND INSTITUTION BUILDING IN CHINA
Authors: Lin Gang 
Published: May 2004

Abstract
Recent leadership transition in China was a mixture of institutional formalization and political personalization. Intra-party democracy has been conducted within the framework of one-party rule and guided by the predetermined principle of democratic centralism. Past choices of rules constrain China's institution building, while providing new opportunities for the reform elite.
Extracting Light from Polymer Light‐Emitting Diodes Using Stamped Bragg Gratings
Authors: Ziebarth J. M. , Saafir A. K. , Fan S. , McGehee M. D. 
Published: May 2004

AbstractIn this paper, we describe a method for increasing the external efficiency of polymer light‐emitting diodes (LEDs) by coupling out waveguided light with Bragg gratings. We numerically model the waveguide modes in a typical LED structure and demonstrate how optimizing layer thicknesses and reducing waveguide absorption can enhance the grating outcoupling. The gratings were created by a soft‐lithography technique that minimizes changes to the conventional LED structure. Using one‐dimensional and two‐dimensional gratings, we were able to increase the forward‐directed emission by 47 % and 70 %, respectively, and the external quantum efficiency by 15 % and 25 %.
Efficient Load Transfer to Polymer‐Grafted Multiwalled Carbon Nanotubes in Polymer Composites
Authors: Hwang G. L. , Shieh Y.‐T. , Hwang K. C. 
Published: May 2004

AbstractMultiwalled carbon nanotubes (MWNTs) grafted with poly(methyl methacrylate) (PMMA) were synthesized by emulsion reactions and used as a reinforcement for commercial PMMA. Both scanning electron microscopy (SEM) and transmission electron microscopy (TEM) revealed that the applied tensile load on the composites was transferred to the PMMA‐grafted MWNTs, leading to a strain failure of the MWNTs rather than an adhesive failure between the MWNTs and the matrix. Dynamic mechanical analysis (DMA) data showed that the storage modulus at 20 °C of the PMMA composite containing 20 wt.‐% of the PMMA‐grafted MWNTs was significantly enhanced by ∼ 29 GPa (or by ∼ 1100 %) as compared with commercial PMMA.
Enhanced Photoelectrochemistry in CdS/Au Nanoparticle Bilayers
Authors: Sheeney‐Haj‐Ichia L. , Pogorelova S. , Gofer Y. , Willner I. 
Published: May 2004

AbstractThree different configurations of Au‐nanoparticle/CdS‐nanoparticle arrays are organized on Au/quartz electrodes for enhanced photocurrent generation. In one configuration, Au‐nanoparticles are covalently linked to the electrode and the CdS‐nanoparticles are covalently linked to the bare Au‐nanoparticle assembly. The resulting photocurrent, φ = 7.5 %, is ca. 9‐fold higher than the photocurrent originating from a CdS‐nanoparticle layer that lacks the Au‐nanoparticles, φ = 0.8 %. The enhanced photocurrent in the Au/CdS nanoparticle array is attributed to effective charge separation of the electron–hole pair by the injection of conduction‐band electrons from the CdS‐ to the Au‐nanoparticles. Two other configurations involving electrostatically stabilized bipyridinium‐crosslinked Au/CdS or CdS/Au nanoparticle arrays were assembled on the Au/quartz crystal. The photocurrent quantum yields in the two systems are φ = 10 % and φ = 5 %, respectively. The photocurrents in control systems that include electrostatically bridged Au/CdS or CdS/Au nanoparticles by oligocationic units that lack electron‐acceptor units are substantially lower than the values observed in the analogous bipyridinium‐bridged systems. The enhanced photocurrents in the bipyridinium‐crosslinked systems is attributed to the stepwise electron transfer of conduction‐band electrons to the Au‐nanoparticles by the bipyridinium relay bridge, a process that stabilizes the electron–hole pair against recombination and leads to effective charge separation.