bluuebunny/crossref_metadata_2025_split huggingface dataset:
5‐Aza‐2′‐deoxycytidine induces p21WAF expression by demethylation of p73 leading to p53‐independent apoptosis in myeloid leukemia
Authors: Schmelz Karin , Wagner Mandy , Dörken Bernd , Tamm Ingo 
Published: December 2004

AbstractThe DNA methylation inhibitor 5‐Aza‐2′‐deoxycytidine (5‐Aza‐CdR) has significant therapeutic value for the treatment of patients with myelodysplastic syndrome (MDS), acute myeloid leukemia (AML) and chronic myeloid leukemia (CML). The demethylating effect of 5‐Aza‐CdR has been well characterized. In contrast, less is known about the molecular events downstream of the methylation inhibition. Here, 5‐Aza‐CdR induced apoptosis in AML cells (both p53 mutant and wild‐type) but not in epithelial or normal PBMCs. Cell death was accompanied by activation of the mitochondrial apoptosis pathway, as shown by release of cytochrome c and AIF and loss of mitochondrial membrane potential (ΔΨm). Activation of caspase‐3 (but not −6 and −8) was detectable using Western blot analysis and measurement of caspase enzymatic activity. 5‐Aza‐CdR treatment resulted in the induction of p21, which correlated with the arrest of AML cells in the G1 cell cycle phase. Induction of p21 expression was independent of its promoter methylation status but mediated by 5‐Aza‐CdR‐induced reexpression of the tumor‐suppressor p73, a known upstream regulator of p21. The p73 promoter was hypermethylated in AML cell lines and in primary AML cells but not in epithelial cells, which were resistant toward 5‐Aza‐CdR. Therefore, 5‐Aza‐CdR‐mediated specific killing of myeloid cells might be dependent on its ability to revert p73 promoter methylation and to reexpress p73 mRNA. In addition, exogenous expression of p73 rendered epithelial cells sensitive to apoptosis induced by 5‐Aza‐CdR or other cytostatic drugs. We therefore conclude that p73 is a relevant target for methylation‐dependent efficacy of 5‐Aza‐CdR in AML cells. © 2004 Wiley‐Liss, Inc.
Identification and validation of novel ERBB2 (HER2, NEU) targets including genes involved in angiogenesis
Authors: Beckers Johannes , Herrmann Felix , Rieger Sandra , Drobyshev Alexei L. , Horsch Marion , Hrabé de Angelis Martin , Seliger Barbara 
Published: December 2004

AbstractV‐erb‐b2 erythroblastic leukemia viral oncogene homolog 2 (ERBB2; synonyms HER2, NEU) encodes a transmembrane glycoprotein with tyrosine kinase‐specific activity that acts as a major switch in different signal‐transduction processes. ERBB2 amplification and overexpression have been found in a number of human cancers, including breast, ovary and kidney carcinoma. Our aim was to detect ERBB2‐regulated target genes that contribute to its tumorigenic effect on a genomewide scale. The differential gene expression profile of ERBB2‐transfected and wild‐type mouse fibroblasts was monitored employing DNA microarrays. Regulated expression of selected genes was verified by RT‐PCR and validated by Western blot analysis. Genomewide gene expression profiling identified (i) known targets of ERBB2 signaling, (ii) genes implicated in tumorigenesis but so far not associated with ERBB2 signaling as well as (iii) genes not yet associated with oncogenic transformation, including novel genes without functional annotation. We also found that at least a fraction of coexpressed genes are closely linked on the genome. ERBB2 overexpression suppresses the transcription of antiangiogenic factors (e.g., Sparc, Timp3, Serpinf1) but induces expression of angiogenic factors (e.g., Klf5, Tnfaip2, Sema3c). Profiling of ERBB2‐dependent gene regulation revealed a compendium of potential diagnostic markers and putative therapeutic targets. Identification of coexpressed genes that colocalize in the genome may indicate gene regulatory mechanisms that require further study to evaluate functional coregulation. (Supplementary material for this article can be found on the International Journal of Cancer website at http://www.interscience.wiley.com/jpages/0020‐7136/suppmat/index.html.) © 2004 Wiley‐Liss, Inc.
Protein from intestinal Eimeria protozoan stimulates IL‐12 release from dendritic cells, exhibits antitumor properties in vivo and is correlated with low intestinal tumorigenicity
Authors: Rosenberg Barnett , Juckett David A. , Aylsworth Charles F. , Dimitrov Nikolay V. , Ho Siu‐Cheong , Judge John W. , Kessel Sarah , Quensen Janet , Wong Kwai‐Pheng Ho , Zlatkin Igor , Zlatkin Tanya 
Published: December 2004

AbstractThe small intestine (SI) of vertebrates exhibits low tumorigenesis and rarely supports metastatic growth from distant tumors. Many theories have been proposed to address this phenomenon, but none has been consistently supported. One candidate mechanism is that the vast immunologic compartment of the SI provides a heightened level of tumor immunosurveillance. Consistent with this, we have identified a molecule of low abundance from bovine SI that has the hallmarks of a potent immunostimulant and may be associated with the natural suppression of cancer in the intestinal tract. The protein originates from an endemic gut protozoan, Eimeria spp., and is homologous to the antigen 3‐1E previously isolated from the avian apicomplexan E. acervulina. We show here that it is a very potent stimulator of IL‐12 release from dendritic cells, upregulates inflammatory modulators in vivo (IL‐12, MCP‐1, IL‐6, TNF‐α and INF‐γ) and has antitumor properties in mice. In addition, it is synergistic in vitro with anti‐CD40 antibody, IFN‐γ, IL‐4 and GM‐CSF; is active across species barriers in vivo; and has no observable toxicity. Based on these activities, we speculate that it is an inducer of protozoan‐targeted innate immunity, which may explain its potential benefit to the intestinal tract and potency as an agent in cancer immunotherapy. © 2004 Wiley‐Liss, Inc.
Growth inhibition of experimental non‐Hodgkin's lymphomas with the targeted cytotoxic somatostatin analogue AN‐238
Authors: Keller Gunhild , Engel Jörg B. , Schally Andrew V. , Nagy Attila , Hammann Brian , Halmos Gabor 
Published: December 2004

AbstractThe cytotoxic analogue of somatostatin, AN‐238, consisting of 2‐pyrrolinodoxorubicin (AN‐201), a superactive derivative of doxorubicin (DOX), linked to somatostatin analogue carrier RC‐121 binds with high affinity to receptors for somatostatin and can be targeted to tumors that express these receptors. Because somatostatin receptors are found in a high percentage of human non‐Hodgkin's lymphomas (NHLs), we evaluated the antitumor effect of AN‐238 in 2 human NHL cell lines in vivo. Nude mice bearing xenografts of RL and HT human NHL were treated with AN‐238 or its components at equimolar doses, and antitumor effects were determined. Expression of mRNA for somatostatin receptor subtypes was measured by RT‐PCR, and the presence of somatostatin receptors was determined by radioligand binding. Toxicity was evaluated by following white blood cell count (WBC) and body weight. AN‐238 significantly (p < 0.05) inhibited growth of RL and HT xenografts and prolonged the tumor doubling time. Cytotoxic radical AN‐201, the unconjugated mixture of somatostatin analogue RC‐121 and AN‐201 or RC‐121 alone had no significant effects. Blockade of somatostatin receptors by excess RC‐121 abolished the effect of AN‐238, demonstrating targeting. Expression of somatostatin receptors was not changed after repeated treatment with AN‐238. AN‐201, but not AN‐238, significantly lowered the WBC and caused a greater decrease in body weight than AN‐238. Our findings demonstrate that targeted chemotherapy with AN‐238 can strongly inhibit the growth of NHL cells, which express somatostatin receptors. AN‐238 could be considered for the treatment for patients with NHL. © 2004 Wiley‐Liss, Inc.
Farnesyltransferase inhibitor SCH‐66336 downregulates secretion of matrix proteinases and inhibits carcinoma cell migration
Authors: Desrosiers Richard R. , Cusson Marie‐Hélène , Turcotte Sandra , Béliveau Richard 
Published: December 2004

AbstractThe ras oncogenes are among those most frequently found in human cancers. Blocking Ras farnesylation is a promising strategy for arresting cancer growth. Ras activates several signaling pathways with key roles in cellular proliferation, invasion, metastasis and angiogenesis. Furthermore, proteolytic activities of matrix proteinases such as urokinase‐type plasminogen activator (uPA) and matrix metalloproteinases (MMPs) are regulated by Ras isoforms. Thus, we investigated the effects of SCH‐66336, a farnesyltransferase inhibitor, on secretion of components of the plasminogen activation system as well as on the gelatinases MMP‐2 and MMP‐9, which play pivotal roles in matrix remodeling. SCH‐66336 up to 5 μM did not significantly alter the viability of prostate (PC‐3) and renal (Caki‐1) cancer cells incubated in serum‐depleted medium. SCH‐66336 partly inhibited the processing of H‐Ras, while levels of mature N‐Ras and K‐Ras remained unaffected. Under these noncytotoxic conditions, uPA and tPA levels were lowered in culture medium but raised in cell lysates, suggesting inhibition of trafficking pathways. In contrast, SCH‐66336 had no effect on uPAR expression or on secreted PAI‐1 levels. As expected, the reduction of uPA and tPA activities by SCH‐66336 inhibited the conversion of plasminogen to plasmin by about 25% in PC‐3 cells. SCH‐66336 also inhibited the levels of secreted pro‐MMP‐2 and pro‐MMP‐9 as well as the release of their inhibitors TIMP‐1 and TIMP‐2. SCH‐66336 decreased both the adhesion and even more so the migration of PC‐3 cells on gelatin. Thus, SCH‐66336 inhibited farnesylation in both cancer cell types, and H‐Ras functions should be reduced by the drug. In addition, the lower levels of secreted proteinases in the presence of SCH‐66336 suggest that reduced matrix remodeling and cell migration should occur in treated tumors. © 2004 Wiley‐Liss, Inc.
A critical comparison of methods for the determination of the aging sensitivity in biomedical grade yttria‐stabilized zirconia
Authors: Deville Sylvain , Gremillard Laurent , Chevalier Jérôme , Fantozzi Gilbert 
Published: December 2004

AbstractSince the recent failure events of two particular series of zirconia femoral heads for total hip replacement prosthesis, a large decrease in the use of zirconia ceramics for orthopaedic implants has been observed. In spite of the biomedical success of this material during the last 10 years, this decrease in use was required for safety reasons, until the cause of the failures is known. It has been shown that these failures were related to the low temperature hydrothermal degradation (also known as aging). Thus, it is crucial to better understand the aging behavior, in order to be able to assess its importance and then control it if required. In this study, various techniques relevant to assess the hydrothermal degradation sensitivity of biomedical grade yttria‐stabilized zirconia are discussed and compared. The expected outputs of conventional methods, that is, X‐ray diffraction and scanning electron microscopy are examined. More recent methods like optical interferometry and atomic force microscopy are presented, with their respective benefits and drawbacks. An up‐to‐date comparison of these different techniques is provided, and their use for ensuring the long‐term reliability of a particular batch of zirconia in terms of aging degradation is demonstrated. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 72B: 239–245, 2005
Emerging methods for providing clinicians with timely feedback on treatment effectiveness: An introduction
Authors: Lambert Michael J. 
Published: December 2004

AbstractThis article introduces the issue of Journal of Clinical Psychology/In Session devoted to the need for, and value of, providing psychotherapists with feedback about client progress during the course of treatment. After an introduction that sets articles in the series in the context of improving psychotherapy outcome, the seven articles in this special issue are briefly summarized. The articles that follow this introduction provide general principles for effective feedback, highlight therapist difficulties in predicting treatment failure, provide “lab tests” for recognition of poorly responding clients, and demonstrate the powerful effects of providing therapists with feedback on client progress. The articles argue that coupling of statistical modeling techniques with currently available information technology is an innovation to routine clinical practice that clinicians can ill afford to overlook. © 2004 Wiley Periodicals, Inc. J Clin Psychol/In Session.
A lab test and algorithms for identifying clients at risk for treatment failure
Authors: Hannan Corinne , Lambert Michael J. , Harmon Cory , Nielsen Stevan Lars , Smart David W. , Shimokawa Kenichi , Sutton Scott W. 
Published: December 2004

AbstractMany branches of medicine rely heavily on lab tests to monitor client treatment response and use this information to modify their treatment. By contrast, those who offer psychological interventions seldom rely on formal assessments (lab tests) to monitor their clients' response to treatment. Data are presented that demonstrate that clinicians rarely accurately predict who will not benefit from psychotherapy. This finding is contrasted with the use of a questionnaire (lab test data) and decision rules on the basis of a client's expected progress. Results have indicated that formal methods of monitoring were able to identify 100% of the patients whose condition had deteriorated at termination, and 85% by the time they had attended three treatment sessions. Practitioners are encouraged to consider formal methods of identifying the deteriorating client. © 2004 Wiley Periodicals, Inc. J Clin Psychol/In Session.
The partners for change outcome management system
Authors: Miller Scott D. , Duncan Barry L. , Sorrell Ryan , Brown George S. 
Published: December 2004

AbstractA number of systems provide feedback regarding client progress and experience of the therapeutic alliance to clinicians. Available evidence indicates that access to such data improves retention and outcome for clients most at risk for treatment failure. Over the last several years, the team at the Institute for the Study of Therapeutic Change has worked to develop an outcome management system that not only provides valid and reliable feedback, but also is as user‐friendly as possible for therapists and consumers. In this article, we describe the system and summarize current research findings. © 2004 Wiley Periodicals, Inc. J Clin Psychol/In Session.
Feedback in psychotherapy
Authors: Claiborn Charles D. , Goodyear Rodney K. 
Published: December 2004

AbstractFeedback is defined as a response to an action that shapes or adjusts that action in subsequent performance. Though its pervasiveness in human behavior is noted, feedback in clinical practice is a deliberate psychological intervention that has two essential functions, information and influence. Feedback can be descriptive, evaluative, emotional, and interpretive. The role of feedback in promoting change through interpersonal influence and the role of resistance in the feedback process are discussed. We present practical examples and suggestions for maximizing the effectiveness of feedback and responding therapeutically to resistance. Current outcome research on feedback as a major component of treatment is reviewed and discussed. Implications of the feedback literature for practice are provided. © 2004 Wiley Periodicals, Inc. J Clin Psychol/In Session.
Providing feedback to psychotherapists on their patients' progress: Clinical results and practice suggestions
Authors: Lambert Michael J. , Harmon Cory , Slade Karstin , Whipple Jason L. , Hawkins Eric J. 
Published: December 2004

AbstractWe describe and illustrate our system to measure, monitor, and feed back information about patient treatment. This clinical innovation relies on research‐based clinical decision tools that provide psychotherapists with timely warnings when a patient's deviation from an expected treatment response foretells possible treatment failure. We summarize the results of four controlled studies using this methodology; the collective results suggest that measuring, monitoring, and predicting treatment failure (feedback) enhance treatment outcomes for patients who have a negative response. Clinicians are encouraged to employ these methods in routine practice despite their confidence in their own ability to predict patient outcome. © 2004 Wiley Periodicals, Inc. J Clin Psychol/In Session.
On Dirichlet's principle and Poincaré's méthode de balayage
Authors: Hildebrandt Stefan 
Published: December 2004

AbstractA short proof is given for the fact that the minimizer of Dirichlet's integral continuously assumes continuous boundary values at regular boundary points. (© 2005 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
On the number of the cusps of cuspidal plane curves
Authors: Tono Keita 
Published: December 2004

AbstractIn this paper, we estimate an upper bound of the number of the cusps of a cuspidal plane curve. We prove that a cuspidal plane curve of genus g has no more than (21g +17)/2 cusps. For example, a rational cuspidal plane curve has no more than 8 cusps and an elliptic one has no more than 19 cusps. (© 2005 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Homogenization of the Neumann problem in thick multi‐structures of type 3 : 2 : 2
Authors: De Maio U. , Mel'nyk T. A. 
Published: December 2004

AbstractUsing some special extension operator, a convergence theorem is proved for the solution to the Neumann boundary value problem for the Ukawa equation in a junction Ωε, which is the union of a domain Ω0 and a large number N of ε‐periodically situated thin annular disks with variable thickness of order ε=𝒪(N‐1), as ε → 0. Copyright © 2004 John Wiley & Sons, Ltd.
Enhanced reinnervation after neurotization with Schwann cell transplantation
Authors: Fukuda Aki , Hirata Hitoshi , Akeda Koji , Morita Akimasa , Nagakura Takeshi , Tsujii Masaya , Uchida Atsumasa 
Published: December 2004

AbstractWe investigated the feasibility of using Schwann cell transplantation to enhance reinnervation after direct nerve‐to‐muscle neurotization (NMN). The denervated anterior tibial muscle was neurotized by tibial nerve implantation, and Schwann cell suspension (transplantation group) or an equivalent volume of culture medium (control group) was injected at the implantation site. In the control group, few axons invaded the muscle, demonstrating that skeletal muscle was poorly permissive to the advancement of axons. In the transplantation group, a large number of regenerating axons grew for a longer distance throughout the muscle, and reinnervated motor endplates were significantly more abundant. Enhanced reinnervation and functional recovery of the muscle in the transplantation group was confirmed by a significant increase in the compound muscle action potential and in muscle weight. These results suggest that intramuscular Schwann cell transplantation has potential as a cell therapy to improve functional recovery after NMN. Muscle Nerve, 2005
Use of muscle fibrillation for tracking nerve regeneration
Authors: Heaton James T. , Kobler James B. 
Published: December 2004

AbstractIndividual muscle fibers in denervated muscle demonstrate repetitive, spontaneous contraction. Such fibrillation activity disappears in denervated muscle if reinnervation occurs, but this relationship has not been formally studied. To test whether the disappearance of fibrillation can be used to track nerve regeneration, we quantified the presence and subsequent disappearance of electromyographic (EMG) fibrillation potentials and fibrillation‐related movement in the rat tongue after unilateral hypoglossal nerve crush at two locations. In mice, fibrillation movement of vibrissae were monitored after unilateral facial nerve crush and compared with the return of symmetrical vibrissae sweeping movements. In both of these rodent cranial motor systems, there was a conspicuous loss of fibrillation at a time when reinnervation is known to take place, suggesting that the visual appearance of fibrillation‐related movement can be used as a simple, noninvasive means of tracking nerve regeneration in these popular experimental motor systems. Muscle Nerve, 2005
Enhanced transverse shear strain shell formulation applied to large elasto‐plastic deformation problems
Authors: Fontes Valente R. A. , Parente M. P. L. , Natal Jorge R. M. , César de Sá J. M. A. , Grácio J. J. 
Published: December 2004

AbstractIn this work, a previously proposed Enhanced Assumed Strain (EAS) finite element formulation for thin shells is revised and extended to account for isotropic and anisotropic material non‐linearities. Transverse shear and membrane‐locking patterns are successfully removed from the displacement‐based formulation. The resultant EAS shell finite element does not rely on any other mixed formulation, since the enhanced strain field is designed to fulfil the null transverse shear strain subspace coming from the classical degenerated formulation. At the same time, a minimum number of enhanced variables is achieved, when compared with previous works in the field. Non‐linear effects are treated within a local reference frame affected by the rigid‐body part of the total deformation. Additive and multiplicative update procedures for the finite rotation degrees‐of‐freedom are implemented to correctly reproduce mid‐point configurations along the incremental deformation path, improving the overall convergence rate. The stress and strain tensors update in the local frame, together with an additive treatment of the EAS terms, lead to a straightforward implementation of non‐linear geometric and material relations. Accuracy of the implemented algorithms is shown in isotropic and anisotropic elasto‐plastic problems. Copyright © 2004 John Wiley & Sons, Ltd.
Preparation and electromagnetic interference shielding characteristics of novel carbon‐nanotube/siloxane/poly‐(urea urethane) nanocomposites
Authors: Ma Chen‐Chi M. , Huang Yuan‐Li , Kuan Hsu‐Chiang , Chiu Yie‐Shun 
Published: December 2004

AbstractPoly(urea urethane) (PUU) with a poly(dimethylsiloxane) soft segment was synthesized. Different types of conductive fillers—carbon nanotube (CNT), silver‐coated carbon nanotube (CNT–Ag), and nickel‐coated carbon nanotube (CNT–Ni)—were blended with PUU to form partially conductive polymer composites. The results showed that highly conductive metals could improve the conductivity of CNTs significantly. When the filler contents were 3, 4, and 5 parts per hundred parts of resin (phr), the PUU/CNT composites possessed electromagnetic interference shielding effectiveness (SE) at 8.5, 28.4, and 26.0 dB as the electromagnetic wave frequencies were 12.3, 16.2, and 15.9 GHz, respectively. SE of the composites that contained CNT–Ni and CNT–Ag increased with the filler loading. At the same modified‐CNT loading, the CNT–Ni‐filled composites had a higher SE than those filled with CNT–Ag. Tensile stresses ranged from 5.7 to 15.6 MPa (a 177.3% increase) when the CNT concentration reached 8 phr. © 2004 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 43: 345–358, 2005
Conservation of cis prolyl bonds in proteins during evolution
Authors: Lorenzen Stephan , Peters Björn , Goede Andrean , Preissner Robert , Frömmel Cornelius 
Published: December 2004

AbstractIn proteins and peptides, the vast majority of peptide bonds occurs in trans conformation, but a considerable fraction (about 5%) of X‐Pro bonds adopts the cis conformation. Here we study the conservation of cis prolyl residues in evolutionary related proteins. We find that overall, in contrast to local, protein sequence similarity is a clear indicator for the conformation of prolyl residues. We observe that cis prolyl residues are more often conserved than trans prolyl residues, and both are more conserved than the surrounding amino acids, which show the same extent of conservation as the whole protein. The pattern of amino acid exchanges differs between cis and trans prolyl residues. Also, the cis prolyl bond is maintained in proteins with sequence identity as low as 20%. This finding emphasizes the importance of cis peptide bonds in protein structure and function. Proteins 2005. © 2004 Wiley‐Liss, Inc.