bluuebunny/crossref_metadata_2025_split huggingface dataset:
The oncoprotein NPM-ALK of anaplastic large-cell lymphoma induces JUNB transcription via ERK1/2 and JunB translation via mTOR signaling
Authors: Staber Philipp B. , Vesely Paul , Haq Naznin , Ott Rene G. , Funato Kotaro , Bambach Isabella , Fuchs Claudia , Schauer Silvia , Linkesch Werner , Hrzenjak Andelko , Dirks Wilhelm G. , Sexl Veronika , Bergler Helmut , Kadin Marshall E. , Sternberg David W. , Kenner Lukas , Hoefler Gerald 
Published: August 2007

AbstractAnaplastic large cell lymphomas (ALCLs) are highly proliferating tumors that commonly express the AP-1 transcription factor JunB. ALK fusions occur in approximately 50% of ALCLs, and among these, 80% have the t(2;5) translocation with NPM-ALK expression. We report greater activity of JunB in NPM-ALK–positive than in NPM-ALK–negative ALCLs. Specific knockdown of JUNB mRNA using small interfering RNA and small hairpin RNA in NPM-ALK–expressing cells decreases cellular proliferation as evidenced by a reduced cell count in the G2/M phase of the cell cycle. Expression of NPM-ALK results in ERK1/2 activation and transcriptional up-regulation of JUNB. Both NPM-ALK–positive and –negative ALCL tumors demonstrate active ERK1/2 signaling. In contrast to NPM-ALK–negative ALCL, the mTOR pathway is active in NPM-ALK–positive lymphomas. Pharmacological inhibition of mTOR in NPM-ALK–positive cells down-regulates JunB protein levels by shifting JUNB mRNA translation from large polysomes to monosomes and ribonucleic particles (RNPs), and decreases cellular proliferation. Thus, JunB is a critical target of mTOR and is translationally regulated in NPM-ALK–positive lymphomas. This is the first study demonstrating translational control of AP-1 transcription factors in human neoplasia. In conjunction with NPM-ALK, JunB enhances cell cycle progression and may therefore represent a therapeutic target.
Is air travel safe for those with lung disease?
Authors: Coker R. K. , Shiner R. J. , Partridge M. R. 
Published: August 2007

Airlines commonly report respiratory in-flight emergencies; flight outcomes have not been examined prospectively in large numbers of respiratory patients. The current authors conducted a prospective, observational study of flight outcomes in this group.UK respiratory specialists were invited to recruit patients planning air travel. Centres undertook their usual pre-flight assessment. Within 2 weeks of returning, patients completed a questionnaire documenting symptoms, in-flight oxygen use and unscheduled healthcare use.In total, 616 patients were recruited. Of these, 500 (81%) returned questionnaires. The most common diagnoses were airway (54%) and diffuse parenchymal lung disease (23%). In total, 12 patients died, seven before flying and five within 1 month. Pre-flight assessment included oximetry (96%), spirometry (95%), hypoxic challenge (45%) and walk test (10%). Of the patients, 11% did not fly. In those who flew, unscheduled respiratory healthcare use increased from 9% in the 4 weeks prior to travel to 19% in the 4 weeks after travel. However, when compared with self-reported data during the preceding year, medical consultations increased by just 2%.In patients flying after careful respiratory specialist assessment, commercial air travel appears generally safe.
Isolated right ventricular dysfunction in systemic sclerosis: latent pulmonary hypertension?
Authors: Huez S. , Roufosse F. , Vachiéry J-L. , Pavelescu A. , Derumeaux G. , Wautrecht J-C. , Cogan E. , Naeije R. 
Published: August 2007

Right ventricular function is frequently abnormal in patients with systemic sclerosis, but whether this is related to pulmonary vascular complications of the disease is unclear.Standard echocardiography with tissue Doppler imaging was performed at rest and during exercise for the study of right ventricular function and pulmonary circulation in 25 consecutive systemic sclerosis patients and in 13 age-matched healthy controls.When compared with the controls, the patients had no difference in systolic right ventricular pressure gradient, but a decreased pulmonary flow acceleration time, and increased right ventricular free wall thickness and end-diastolic dimensions. At the tricuspid annulus, the E maximal velocity was decreased (8.9±4versus11.7±2.3 cm·s−1) and the isovolumic relaxation time corrected to RR interval was increased (6.5±2.9versus4.5±2.5%). The tissue Doppler imaging profile at the mitral annulus was similar in both groups. At exercise, 18 patients had a decreased maximum workload and cardiac output, no change in systolic right ventricular pressure gradient, but an increase in the slope of pulmonary artery pressure/flow relationships.These results suggest that patients with systemic sclerosis may present with latent pulmonary hypertension as a likely cause of right ventricular diastolic dysfunction, as revealed by stress echocardiography and tissue Doppler imaging.
Chemotherapy improves low performance status lung cancer patients
Authors: Sculier J. P. , Lafitte J. J. , Paesmans M. , Lecomte J. , Alexopoulos C. G. , Van Cutsem O. , Giner V. , Efremidis A. , Berchier M. C. , Collon T. , Meert A. P. , Scherpereel A. , Ninane V. , Koumakis G. , Vaslamatzis M. M. , Leclercq N. , Berghmans T. 
Published: August 2007

The aim of the present study was to determine the potential benefit of conventional cisplatin-based chemotherapy on patients with advanced nonsmall cell lung cancer (NSCLC) and poor performance status (PS), defined as 60–70 on the Karnofsky scale.Retrospective analysis was carried out of a randomised trial performed in advanced NSCLC where 485 patients received three courses of gemcitabine+ifosfamide+cisplatin induction chemotherapy.Of the patients, 80% had good PS (Karnofsky 80–100) and 20% poor PS. Response rates were 38 and 28%, respectively. Clinical improvement, defined as achieving a good PS during chemotherapy, was observed overall in 25% of the poor PS patients, with rates of 38, 20 and 14%, respectively, in case of response, no change and progression. PS improved more quickly in the responders. Survival of patients with poor PS was significantly worse, but survival of responders was similar, irrespective of the initial poor or good PS. Although nonfatal toxicity was almost similar, there were more toxic deaths (including vascular and cardiac fatalities) in the poor PS patients (9.2versus2.1%).In conclusion, combination chemotherapy is associated with clinical improvement in a substantial number of patients with advanced nonsmall cell lung cancer of poor performance status.
Long-term treatment with sildenafil in chronic thromboembolic pulmonary hypertension
Authors: Reichenberger F. , Voswinckel R. , Enke B. , Rutsch M. , El Fechtali E. , Schmehl T. , Olschewski H. , Schermuly R. , Weissmann N. , Ghofrani H. A. , Grimminger F. , Mayer E. , Seeger W. 
Published: August 2007

For chronic thromboembolic pulmonary hypertension not amenable to pulmonary endarterectomy, effective medical therapy is desired.In an open-label uncontrolled clinical trial, 104 patients (mean±semage 62±11 yrs) with inoperable chronic thromboembolic pulmonary hypertension were treated with 50 mg sildenafilt.i.d.At baseline, patients had severe pulmonary hypertension (pulmonary vascular resistance 863±38 dyn·s·cm−5) and a 6-min walking distance of 310±11 m. Eight patients were in World Health Organization functional class II, 76 in class III and 20 in class IV.After 3 months’ treatment, there was significant haemodynamic improvement, with reduction of pulmonary vascular resistance to 759±62 dyn·s·cm−5. The 6-min walking distance increased significantly to 361±15 m after 3 months’ treatment, and to 366±18 m after 12 months’ treatment. A subset of 67 patients received a single dose of 50 mg sildenafil during initial right heart catheterisation. The acute haemodynamic effect of this was not predictive of long-term outcome.In this large series of patients with inoperable chronic thromboembolic pulmonary hypertension, open-label treatment with sildenafil led to significant long-term functional improvement. The acute effect of sildenafil may not predict the long-term outcome of therapy.
Premature discontinuation of patients: a potential bias in COPD clinical trials
Authors: Kesten S. , Plautz M. , Piquette C. A. , Habib M. P. , Niewoehner D. E. 
Published: August 2007

Premature discontinuation from clinical trials may bias results against effective therapies.In the present study mortality rates were retrospectively reviewed in a 6-month, randomised, placebo-controlled trial in which tiotropium 18 μg daily was shown to decrease chronic obstructive pulmonary disease exacerbations. Patients participated for 6 months even if trial medication was prematurely discontinued. Exposure-adjusted incidence rates (IRs) were calculated for randomisation–end trial, randomisation–end trial drug (0–ED) and end trial drug–end trial (ED–ET).Of 1,829 patients (forced expiratory volume in one second 1.04 L (36% predicted), mean age 68 yrs, 99% male), 16% tiotropium and 27% placebo patients prematurely stopped trial medication. The number of fatal events for the entire cohort was: 62 all cause, including 16 cardiac and 16 lower respiratory. IRs for fatal events per 100 patient-yrs were higher in the discontinued period: 1.9 (0–ED)versus23.0 (ED–ET) in the tiotropium group and 1.8versus19.0 in the placebo group. Respective IRs for fatal cardiac events were 0.7versus2.8 (tiotropium) and 0.5versus6.2 (placebo); for fatal lower respiratory events were 0.7versus2.8 (tiotropium) and 0.8versus5.4 (placebo). Rate ratios (tiotropium/placebo) for fatal events were lower in the discontinued period: 1.4versus0.5 for cardiac and 0.9versus0.5 for lower respiratory.Higher incidence rates of fatal events occurred following premature discontinuation of study medication. Incomplete information from rate ratios occurs as a result of failure to consider outcomes of patients who discontinue early from clinical trials.
Analgesic and anti-inflammatory drug use and risk of bladder cancer: a population based case control study
Authors: Fortuny Joan , Kogevinas Manolis , Zens Michael S , Schned Alan , Andrew Angeline S , Heaney John , Kelsey Karl T , Karagas Margaret R 
Published: August 2007

Abstract

Background
Use of phenacetin and other analgesic and non-steroidal anti-inflammatory drugs (NSAIDs) potentially influences bladder cancer incidence, but epidemiologic evidence is limited.

Methods
We analyzed data from 376 incident bladder cancer cases and 463 controls from a population-based case-control study in New Hampshire on whom regular use of analgesic drugs and NSAIDs was obtained. Odds ratios and 95% confidence intervals were computed using logistic regression with adjustment for potentially confounding factors. Separate models by tumor stage, grade and TP53 status were conducted.

Results
We found an elevated odds ratio (OR) associated with reported use of phenacetin-containing medications, especially with longer duration of use (OR >8 years = 3.00, 95% confidence interval (CI) = 1.4–6.5). In contrast, use of paracetamol did not relate overall to risk of bladder cancer. We also found that regular use of any NSAID was associated with a statistically significant decrease in bladder cancer risk (OR = 0.6, 95% CI = 0.4–0.9), and specifically use of aspirin. Further, the association with NSAID use was largely among invasive, high grade and TP53 positive tumors.

Conclusion
While these agents have been investigated in several studies, a number of questions remain regarding the effects of analgesic and NSAID use on risk of bladder cancer.
Proteomic analysis of plasma membrane and secretory vesicles from human neutrophils
Authors: Jethwaney Deepa , Islam Md Rafiqul , Leidal Kevin G , de Bernabe Daniel Beltran-Valero , Campbell Kevin P , Nauseef William M , Gibson Bradford W 
Published: August 2007

AbstractBackgroundPolymorphonuclear neutrophils (PMN) constitute an essential cellular component of innate host defense against microbial invasion and exhibit a wide array of responses both to particulate and soluble stimuli. As the cells recruited earliest during acute inflammation, PMN respond rapidly and release a variety of potent cytotoxic agents within minutes of exposure to microbes or their products. PMN rely on the redistribution of functionally important proteins, from intracellular compartments to the plasma membrane and phagosome, as the means by which to respond quickly. To determine the range of membrane proteins available for rapid recruitment during PMN activation, we analyzed the proteins in subcellular fractions enriched for plasma membrane and secretory vesicles recovered from the light membrane fraction of resting PMN after Percoll gradient centrifugation and free-flow electrophoresis purification using mass spectrometry-based proteomics methods.ResultsTo identify the proteins light membrane fractions enriched for plasma membrane vesicles and secretory vesicles, we employed a proteomic approach, first using MALDI-TOF (peptide mass fingerprinting) and then by HPLC-MS/MS using a 3D ion trap mass spectrometer to analyze the two vesicle populations from resting PMN. We identified several proteins that are functionally important but had not previously been recovered in PMN secretory vesicles. Two such proteins, 5-lipoxygenase-activating protein (FLAP) and dysferlin were further validated by immunoblot analysis.ConclusionOur data demonstrate the broad array of proteins present in secretory vesicles that provides the PMN with the capacity for remarkable and rapid reorganization of its plasma membrane after exposure to proinflammatory agents or stimuli.
A continuum mathematical model of endothelial layer maintenance and senescence
Authors: Wang Ying , Aguda Baltazar D , Friedman Avner 
Published: August 2007

Abstract

Background
The monolayer of endothelial cells (ECs) lining the inner wall of blood vessels deteriorates as a person ages due to a complex interplay of a variety of causes including cell death arising from shear stress of blood flow and cellular oxidative stress, cellular senescence, and decreased rate of replacement of dead ECs by progenitor stem cells.

Results
A continuum mathematical model is developed to describe the dynamics of large EC populations of the endothelium using a system of differential equations for the number densities of cells of different generations starting from endothelial progenitors to senescent cells, as well as the densities of dead cells and the holes created upon clearing dead cells. Aging of cells is manifested in three ways, namely, losing the ability to divide when the Hayflick limit of 50 generations is reached, decreasing replication rate parameters and increasing death rate parameters as cells divide; due to the dependence of these rate parameters on cell generation, the model predicts a narrow distribution of cell densities peaking at a particular cell generation. As the chronological age of a person advances, the peak of the distribution – corresponding to the age of the endothelium – moves towards senescence correspondingly. However, computer simulations also demonstrate that sustained and enhanced stem cell homing can halt the aging process of the endothelium by maintaining a stationary cell density distribution that peaks well before the Hayflick limit. The healing rates of damaged endothelia for young, middle-aged, and old persons are compared and are found to be particularly sensitive to the stem cell homing parameter.

Conclusion
The proposed model describes the aging of the endothelium as being driven by cellular senescence, with a rate that does not necessarily correspond to the chronological aging of a person. It is shown that the age of the endothelium depends sensitively on the homing rates of EC progenitor cells.
GnRH and LHRgene variants predict adverse outcome in premenopausal breast cancer patients
Authors: Piersma Djura , Themmen Axel PN , Look Maxime P , Klijn Jan GM , Foekens John A , Uitterlinden André G , Pols Huibert AP , Berns Els MJJ 
Published: August 2007

Abstract
Background
Breast cancer development and progression are dependent on estrogen activity. In premenopausal women, estrogen production is mainly regulated through the hypothalamic-pituitary-gonadal (HPG) axis.

Methods
We have investigated the prognostic significance of two variants of genes involved in the HPG-axis, the GnRH (encoding gonadotropin-releasing hormone) 16Trp/Ser genotype and the LHR (encoding the luteinizing hormone receptor) insLQ variant, in retrospectively collected premenopausal breast cancer patients with a long follow-up (median follow-up of 11 years for living patients).

Results
Carriership was not related with breast cancer risk (the case control study encompassed 278 premenopausal cases and 1,758 premenopausal controls). A significant adverse relationship of the LHR insLQ and GnRH 16Ser genotype with disease free survival (DFS) was observed in premenopausal (hormone receptor positive) breast cancer patients. In particular, those patients carrying both the GnRH 16Ser and LHR insLQ allele (approximately 25%) showed a significant increased risk of relapse, which was independent of traditional prognostic factors (hazard ratio 2.14; 95% confidence interval 1.32 to 3.45; P = 0.002).

Conclusion
We conclude that the LHR insLQ and GnRH 16Ser alleles are independently associated with shorter DFS in premenopausal patients. When validated, these findings may provide a lead in the development of tailored treatment for breast cancer patients carrying both polymorphisms.
Understanding Clusters toward the Design of Functional Molecules and Nanomaterials
Authors: Singh N Jiten , Lee Eun Cheol , Choi Young Cheol , Lee Han Myoung , Kim Kwang S 
Published: August 2007

Abstract
In this account, we highlight the theoretical investigations of various cluster systems comprising of water clusters, π-containing clusters, and metallic clusters. We illustrate how these investigations help us understand and design structures and properties of nanowires, novel functional ionophores/receptors, and nanomaterials. Many of these theoretically predicted systems have been experimentally realized and some of the predicted structures/properties are left for the future which of course could be promising challenges for experimentalists.
Chiral Glycolate Equivalents for the Asymmetric Synthesis of α-Hydroxycarbonyl Compounds
Authors: Ley Steven V , Sheppard Tom D , Myers Rebecca M , Chorghade Mukund S 
Published: August 2007

Abstract
Chiral glycolic acid equivalents are used extensively for the enantioselective synthesis of α-hydroxycarbonyl compounds. Their efficacy in enolate reactions and their utility in synthetic applications are discussed, highlighting the relevance of these methods to natural product synthesis.
Energy-Transfer Mechanism in Photoluminescent Terbium(III) Complexes Causing Their Temperature-Dependence
Authors: Katagiri Shinya , Tsukahara Yasunori , Hasegawa Yasuchika , Wada Yuji 
Published: August 2007

Abstract
Photoluminescence of Terbium(III) complexes was investigated as a function of temperatures in the range of 80–280 K for [Tb(bfa)3(H2O)2] (bfa: 4,4,4-trifluoro-1-phenyl-1,3-butanedionato), [Tb(hfa)3(H2O)3] (hfa: hexafluoroacetylacetonato), [Tb(tfa)3(H2O)2] (tfa: trifluoroacetylacetonato), [Tb(acac)3(H2O)3] (acac: acetylacetonato), and [Tb(hfa)3(tppo)2] (tppo: triphenylphosphine oxide). These complexes were classified into the two groups with different temperature-dependences. The first group consisting of [Tb(bfa)3(H2O)2], [Tb(tfa)3(H2O)2], and [Tb(acac)3(H2O)3] showed a dependence determined by the energy gap between the excited triplet state of the ligand and the emitting level of terbium(III) ion. In contrast, for [Tb(hfa)3(H2O)3] and [Tb(hfa)3(tppo)2] containing hfa as a ligand, not only the energy gap but also the energy barriers of the “Forward energy transfer” from the ligand to terbium(III) ion and “Back energy transfer” from terbium(III) ion to the ligand were taken into account for understanding their dependences. These results are discussed based on the re-orientation of the complexes accompanied by the forward and back energy transfer processes using DFT calculations.
Voltammetric Study of Two-Dimensional Phase-Transition Processes of Carboxylated Viologens at an HOPG Electrode as a Typical Organization Process of Molecules Possessing Multiple Interaction Sites
Authors: Tanaka Yasuhiko , Sagara Takamasa 
Published: August 2007

Abstract
Two-dimensional (2D) phase-transition behavior of three different viologens, heptyl viologen and its mono- and dicarboxylated derivatives, is described using the results of voltammetric measurements at an HOPG electrode. The transition was regarded as a typical 2D molecular organization process under oxidation state control. In an acidic medium, the width of the bi-stable potential region of the phase-transition was found to increase by approximately 55 mV with each addition of a carboxylate group. This fact points to a dominant contribution from intermolecular hydrogen bonding to the reductive formation of the 2D condensed phase. The occurrence of an incomplete transition process resulting in the formation of a metastable phase at lower temperatures, higher potential sweep rates, and higher concentrations was observed for dicarboxylated viologen, but not for monocarboxylated one. These results were used to discuss the advantages and disadvantages of multiple intermolecular interaction sites in a molecule in relation to the 2D molecular organization processes.
Ternary Inclusion Complexes of γ-Cyclodextrin with Resorufin and Organic Cations in Aqueous Solution
Authors: Hamai Sanyo 
Published: August 2007

Abstract
Molecular interactions of an organic anion, resorufin (Res), with γ-cyclodextrin (γ-CD) and several organic cations were investigated by means of absorption and fluorescence spectroscopy. A 1:1 inclusion complex is formed between γ-CD and Res. In addition, Res forms a 1:1 organic cation–organic anion complex with 1,1′-diheptyl-4,4′-bipyridyl dibromide (DHB) and 1,1′-dimethyl-4,4′-bipyridyl dibromide (DMB), although Res does not form an organic cation–organic anion complex with trimethyloctylammonium bromide (TMOA). The γ-CD–Res inclusion complex forms a ternary inclusion complex with TMOA, DHB, and DMB. The equilibrium constant for the formation of the 1:1:1 γ-CD–Res–TMOA inclusion complex is nearly the same as that of the 1:1:1 γ-CD–Res–DHB inclusion complex. On the other hand, the equilibrium constant for the formation of the 1:1:1 γ-CD–Res–DMB inclusion complex is significantly less than that of 1:1:1 γ-CD–Res–DHB inclusion complex. These findings suggest that the long alkyl-chain in the organic cations examined promotes the formation of a ternary inclusion complex of Res.
Synthesis and Electrochemical Properties of Tetranuclear Di-μ-oxo-bis[di-μ-phenolatodiiron(III)] Complexes
Authors: Miyazato Yuji , Ohba Masaaki , Sakiyama Hiroshi , Ōkawa Hisashi 
Published: August 2007

Abstract
A series of tetrairon(III) complexes of di-μ-oxo-bis[di-μ-phenolatodiiron(III)] core, [{Fe2(L)(L′)}2(μ-O)2](PF6)2 (1–11), where L2− is the phenol-based macrocyclic compartmental ligand and (L′)− is acetate, monochloroacetate, dichloroacetate, trifluoroacetate, pentafluoropropionate, benzoate, p-nitrobenzoate, pentafluorobenzoate, diethyl phosphate, diphenyl phosphate, or diethyldithiophosphate for 1–11, respectively, were synthesized. X-ray crystallographic studies for 4, 7, and 9 indicated that two {Fe2(L)(L′)} units were connected by two oxo bridges to afford a tetranuclear di-μ-oxo-bis[di-μ-phenolatodiiron(III)] core. Cyclic voltammograms of 1–11 in acetonitrile showed a quasi-reversible or irreversible reduction wave between −332 and −620 mV (vs. Ag/Ag+), which were attributed to a two-electron process involving the Fe4III,III,III,III/Fe4II,II,III,III. The Fe4III,III,III,III/Fe4II,II,III,III potential shifted positive with a decrease in the electron-donating ability of the end-cap ligand, and a good linear correlation was found between the potentials and the pKa values of HL′. The Fe4II,II,III,III species were generated in acetonitrile by electrochemical reduction and showed broad intervalence transition bands in the range of 900–1500 nm.