bluuebunny/crossref_metadata_2025_split huggingface dataset:
Randomized Phase III Trial of Pegylated Liposomal Doxorubicin Versus Vinorelbine or Mitomycin C Plus Vinblastine in Women With Taxane-Refractory Advanced Breast Cancer
Authors: Keller Alan M. , Mennel Robert G. , Georgoulias Vassilis A. , Nabholtz Jean-Marc , Erazo Aura , Lluch Anna , Vogel Charles L. , Kaufmann Manfred , von Minckwitz Gunther , Henderson I. Craig , Mellars Lillian , Alland Leila , Tendler Craig 
Published: September 2004

Purpose To compare the efficacy of pegylated liposomal doxorubicin (PLD) with that of a common salvage regimen (comparator) in patients with taxane-refractory advanced breast cancer. Patients and Methods Following failure of a first- or second-line taxane-containing regimen for metastatic disease, 301 women were randomly assigned to receive PLD (50 mg/m2 every 28 days); or comparator-vinorelbine (30 mg/m2 weekly) or mitomycin C (10 mg/m2 day 1 and every 28 days) plus vinblastine (5 mg/m2 day 1, day 14, day 28, and day 42) every 6 to 8 weeks. Patients were stratified before random assignment based on number of previous chemotherapy regimens for metastatic disease and presence of bone metastases only. Results Progression-free survival (PFS) and overall survival (OS) were similar for PLD and comparator (PFS: hazard ratio [HR], 1.26; 95% CI, 0.98 to 1.62; P = .11; median, 2.9 months [PLD] and 2.5 months [comparator]; OS: HR, 1.05; 95% CI, 0.82 to 1.33; P = .71; median, 11.0 months [PLD] and 9.0 months [comparator]). In anthracycline-naïve patients, PFS was somewhat longer with PLD, relative to the comparator (n = 44; median PFS, 5.8 v 2.1 months; HR, 2.40; 95% CI, 1.16 to 4.95; P = .01). Most frequently reported adverse events were nausea (23% to 31%), vomiting (17% to 20%), and fatigue (9% to 20%) and were similar among treatment groups. PLD-treated patients experienced more palmar-plantar erythrodysesthesia (37%; 18% grade 3, 1 patient grade 4) and stomatitis (22%; 5% grades 3/4). Neuropathy (11%), constipation (16%), and neutropenia (14%) were more common with vinorelbine. Alopecia was low in both the PLD and vinorelbine groups (3% and 5%). Conclusion PLD has efficacy comparable to that of common salvage regimens in patients with taxane-refractory metastatic breast cancer, thereby representing a useful therapeutic option.
Imitative Games by 9‐, 14‐, and 18‐Month‐Old Infants
Authors: Agnetta Bryan , Rochat Philippe 
Published: September 2004

AbstractTwo experiments used a mutual imitation paradigm to assess 9‐, 14‐, and 18‐month‐old infants' developing understanding of intentions in others. In the first study, 1 experimenter imitated the infants' actions, and another experimenter performed contingent but different actions on an identical toy. From 9 months of age, infants show discrimination between the mimicking and the contingent experimenter. In a second study, same‐age groups of infants faced either an experimenter mimicking their actions on an identical object or the object mimicking them independently of any manual contact by the experimenter. Only 14‐ and 18‐month‐olds showed discrimination between the 2 conditions, this discrimination correlating with infants' relative ability to follow gaze and points in triadic exchanges. These results are interpreted as demonstrating important developmental changes between 9 and 14 months in the construal of others as intentional.
Physiological and Emotional Reactivity to Learning and Frustration
Authors: Lewis Michael , Hitchcock Daniel F. A. , Sullivan Margaret Wolan 
Published: September 2004

AbstractThis study examined the behavioral (arm, facial) and autonomic (heart rate, respiratory sinus arrhythmia [RSA], and adrenocortical axis) reactivity of 56 4‐month‐old infants in response to contingency learning and extinction‐induced frustration. During learning, infants displayed increases in operant arm response and positive emotional expressions. Changes in average RSA(VNA) paralleled the observed changes in facial expressions in general and maintained an inverse relation with heart rate throughout most of the session. When frustrated by extinction, infants displayed increases in negative expressions, heart rate, and a brief increase in RSA(VNA) followed by a significant decrease. No significant changes were observed for Cortisol. These behavioral and facial responses are consistent with earlier work. The physiological changes, along with the facial expressions and instrumental responses, indicate that the autonomic nervous system functions as a coordinated affect system by 4 months of age.
Ultrathin Silica Films with a Nanoporous Monolayer
Authors: Tanaka Shunsuke , Nishiyama Norikazu , Hayashi Yasushi , Egashira Yasuyuki , Ueyama Korekazu 
Published: September 2004

Abstract
Ultrathin silica films with a monolayer of uniform nanopores were fabricated on a silicon substrate by contacting triblock copolymer films with tetraethoxysilane vapor followed by calcination to remove the copolymer.
Stability of Sufentanil Citrate with Levobupivacaine HCl in NaCl 0.9% Infusion After Microwave Freeze–Thaw Treatment
Authors: Boitquin Laurence P , Hecq Jean-Daniel , Vanbeckbergen Danielle F , Jamart Jacques , Galanti Laurence M 
Published: September 2004

BACKGROUND Sufentanil is a powerful central anesthetic and analgesic of the opiate family that can be used with levobupivacaine for epidural administration. Advance preparation of intravenous solution could be useful to improve quality, time management, and cost-savings of drug delivery. OBJECTIVE To investigate how freezing, long-term storage, and microwave thawing can affect the stability of sufentanil citrate and levobupivacaine HCl in NaCl 0.9% (saline) (w/v) polyvinyl chloride (PVC) bags. METHODS The stability of 5 bags of solution containing sufentanil 500 μg and levobupivacaine 625 mg per 500 mL of saline solution in PVC bags was studied after freezing for 4 months at −30 °C, thawing in a microwave oven with a validated cycle, and storage at 4 °C. The concentrations of the drugs were measured by HPLC using a reversed-phase column, a mobile phase consisting of 18% acetonitrile (v/v) in tertabutyl ammonium hydrogen sulfate buffer 0.03 M pH 3.00 ± 0.05, and UV detection at 235 nm for sufentanil and 260 nm for levobupivacaine. Visual inspection and pH measurement were also performed. RESULTS No color change or precipitation was observed. Sufentanil and levobupivacaine were stable for at least 70 days at 4 °C after freezing and thawing. Throughout this period, the 95% lower confidence limit of the concentration–time profile remained >90% of the initial concentration. During this period, the pH value remained stable. CONCLUSIONS Within the limits defined here, a mixture of sufentanil citrate and levobupivacaine HCl may be prepared in advance and kept frozen.
Molecular Models of Acidic PePtides From Pea Bud Chromatin And Seminal Plasma. Divalent Cations-Mediated Interaction With Dna
Authors: Mancinelli L. , Chillemi F. , Cardellini E. , Marsili V. , Giavarini F. , Angelis L. DE , Lugaro G. , Gianfranceschi G.L. 
Published: September 2004

AbstractSmall acidic peptides have been isolated from biological fluids (blood and seminal plasma) and from chromatin of several tissues. Their biological activity is related to the control of cell growth and gene expression.This work is an approach to the study of peptide structure-function relationship. Purified fractions from seminal plasma and pea bud chromatin were subjected to fast ion bombardment mass spectrometry. The results obtained were analyzed according to biochemical characteristics of the peptides studied and some possible molecular models have been designed. Two of the proposed sequences were synthesized and their biological activity assayed in cells and cell-free systems. The results demonstrate that the synthetic peptides are able to bind to DNA in the presence of divalent cations (Mg
Cytidine Triphosphate Synthase Activity and mRNA Expression in Normal Human Blood Cells
Authors: Verschuur A.C. , Gennip A.H. Van , Muller E.J. , Voûte P.A.T. , Vreken P. , Kuilenburg A.B.P. Van 
Published: September 2004

AbstractCytidine triphosphate (CTP) synthase is one of the key enzymes in pyrimidine nucleotide anabolic pathways. The activity of this enzyme is elevated in various malignancies including acute lymphocytic leukemia (ALL). In this study we investigated the activity of CTP synthase in various human blood cells isolated from healthy volunteers by density centrifugation and elutriation centrifugation. We also investigated the mRNA expression of CTP synthase in lymphocytes and monocytes. The highest activity of CTP synthase was found in thrombocytes (6.48 nmol CTP × mg−1× h−1), followed by that of monocytes (2.23), lymphocytes (1.69), granulocytes (0.52) and erythrocytes (0.42). The activity of CTP synthase in whole blood samples was at an intermediate level (1.27). The mRNA expression of CTP synthase in monocytes was comparable to that observed in lymphocytes.
Activation of Protein C by Arginine-Specific Cysteine Proteinases (Gingipains-R) from Porphyromonas gingivalis
Authors: Hosotaki K. , Imamura T. , Potempa J. , Kitamura N. , Travis J. 
Published: September 2004

AbstractIn order to determine the effect of bacterial proteinases on activation of the protein C system, a negative regulator of blood coagulation, two arginine-specific cysteine proteinases (gingipains R) fromPorphyromonas gingivalis, a causative bacterium of adult periodontitis, were examined. Each enzyme activated human protein C in a dose- and incubation time-dependent manner. Interestingly, the form of enzyme being composed of a non-covalent complex containing both catalytic and adhesion domains (RgpA) produced activated protein C 14-fold more efficiently than RgpB which contained the catalytic domain alone. Thekcat/Kmvalue of RgpA was 18-fold higher than that of RgpB and comparable to that of the thrombin-thrombomodulin complex, the physiological activator of protein C. RgpA catalyzed protein C activation was augmented 1.4-fold by phospholipids, ubiquitous cell membrane components. Furthermore, RgpA, but not RgpB, could activate protein C in plasma and this resulted in a decrease of the protein C concentration in plasma, which is often observed in patients with sepsis during the development of disseminated intravascular coagulation (DIC). These data indicate that RgpA is a more potent activator of protein C than RgpB and suggest that only the former enzyme can cause protein C activationin vivo. The present study further suggests that bacterial proteinases may possibly contribute to the consumption of plasma protein C which predisposes to DIC and/or promotes a thrombotic tendency towards DIC in sepsis.
Alteration of Mosaic Methylation of the Repeat Unit of the Human Ribosomal RNA Genes in Lung Cancer
Authors: Shiraishi M. , Sekiguchi A. , Chuu Y.H. , Sekiya T. 
Published: September 2004

AbstractWe have investigated the methylation status of the repeat unit of the human ribosomal RNA genes in lung cancer. Using a Southern blot analysis approach we have determined that the non-transcribed region of these genes was generally heavily methylated, while the transcribed region was not methylated in either tumor or normal DNA. Our study also revealed that, in one tumor, the boundary of mosaic methylation of the repeat unit was not distinct. In the same tumor, both the non-transcribed ribosomal spacer region and the L1 interspersed repeat sequences became partially demethylated. In tumor cells, the methylation status of DNA can be altered, but the methylation of subtelomeric repeats was found to be maintained. These results suggest that the mosaic methylation of the repeat unit is not necessarily maintained in tumor DNA, while subtelomeric repeats escape tumor-specific wave of demethylation.
Degradation of the Cyclic AMP Antagonist Prostaglandylinositol Cyclic Phosphate (Cyclic PIP) by Dephosphorylation
Authors: Kassner A. , Lessmann M. , Wasner H.K. 
Published: September 2004

AbstractThe cAMP antagonist, prostaglandylinositol cyclic phosphate (cyclic PIP), is synthesized from prostaglandin E and activated inositol phosphate. From various tissues only that amount of cyclic PIP can be isolated that constitutes the difference between synthesis and degradation. In order to overcome this drawback, the cyclic PIP degrading enzyme or enzymes had to be characterized prior to searching for inhibitors. Cyclic PIP degrading activities have been found in all rat tissues tested, and are lowest in brain (380 pmol × min
cDNA Sequencing of Guinea Pig a2-HS Glycoprotein, Its Expression in Various Tissues and Acute Phase Expression
Authors: Yoshida K. , Suzuki Y. , Yamamoto K. , Sinohara H. 
Published: September 2004

AbstractcDNA encoding α2-HS glycoprotein was amplified from guinea pig liver mRNA by reverse-transcription polymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends, cloned and sequenced. By RTPCR and nested PCR, α2-HS glycoprotein mRNA was detected not only in liver tissue but also in pancreas, stomach, small intestine, colon, spleen, kidney, testis, skeletal muscle, brain, heart and leukocytes, but not in the lung. The α2-HS glycoprotein mRNA levels in the liver were reduced to half at 48 h after subcutaneous injection of turpentine oil.
Phage Display Selection of P1 Mutants of BPTI Directed against Five Different Serine Proteinases
Authors: Kiczak L. , Koscielska K. , Otlewski J. , Czerwinski M. , Dadlez M. 
Published: September 2004

AbstractThe P1 position of protein inhibitors and oligopeptide substrates determines, to a large extent, association energy with many serine proteinases. To test the agreement of phage display selection with the existing thermodynamic data, a small library of all 20 P1 mutants of basic pancreatic trypsin inhibitor (BPTI) was created, fused to protein III, and displayed on the surface of M13 phage. The wild type of displayed inhibitor monovalently and strongly inhibited trypsin with an association constant of
Lymphocyte Antigen Receptor Signal Integration and Regulation by the SHC Adaptor
Authors: Baldari C.T. , Telford. J.L. 
Published: September 2004

AbstractThe Shc adaptor protein transduces signals from transmembrane receptors to the Ras pathway of cell activation by providing binding sites for the recruitment to the submembrane compartment of the Grb2/Sos G-nucleotide exchange complex. The need for Shc in this process is however unclear since Grb2 can be recruited directly to phosphotyrosine containing membrane receptors through its src-homology-2 domain. Evidence from studies in lymphocytes indicates that Shc is multifunctional and is involved in the integration of independent signals to the Ras pathway. Furthermore, Shc may be a key control point at which signaling can be modulated both by interfering signals and by feedback mechanisms. Here we review recent literature to support these functions for Shc.
New Insights into Signal Recognition and Elongation Arrest Activities of the Signal Recognition Particle
Authors: Bui N. , Strub K. 
Published: September 2004

AbstractThe signal recognition particle (SRP), a ubiquitous cytoplasmic ribonucleoprotein particle, plays an essential role in promoting co-translational translocation of proteins into the endoplasmic reticulum. Here, we summarise recent progress made in the understanding of two essential SRP functions: the signal recognition function, which ensures the specificity, and the elongation arrest function, which increases the efficiency of translocation. Our discussion is based on functional data as well as on atomic structure information, both of which also support the notion that SRP is a very ancient particle closely related to ribosomes. Based on the significant increase of knowledge that has been accumulating on the structure of elongation factors and on their interactions with the ribosome, we speculate about a possible mechanism of the elongation arrest function.
The Epstein-Barr Virus Nuclear Antigen 2 (EBNA2), a Protein Required for B Lymphocyte Immortalization, Induces the Synthesis of Type I Interferon in Burkitts Lymphoma Cell Lines
Authors: Kanda K. , Kempkes B. , Bornkamm G.W. , Gabain A. von , Decker T. 
Published: September 2004

AbstractEpstein-Barr virus nuclear antigen 2 (EBNA2), a protein involved in cell transformation, interferes with the cellular response to type I interferons (IFN-α/β). We investigated the function of conditionally expressed EBNA2 in the context of the IFN response in Burkitt's lymphoma cell lines. Expression of EBNA2 led to the transcriptional activation of both endogenous or transfected IFN-stimulated genes (ISGs), genes which contain within their promoters either the interferon-stimulated response element (ISRE) or the gamma interferon activation site (GAS). In search of a molecular mechanism for the transcriptional induction of ISGs, we observed an EBNA2-dependent synthesis of IFN-β mRNA at low levels and the secretion of low amounts of IFN. A transfected IFN-β promoter responded to EBNA2 activation, and a sequence closely resembling a RBP-Jκ binding site was pinpointed as a potential target of EBNA2 activity. EBNA2-dependent transcriptional induction of the IFN-β promoter occurred in EBV-negative Burkitt's lymphoma cells, indicating that other EBV genes were not required for the induction of IFN-β synthesis.
Regulation of Human c-Abl Tyrosine Kinase Activity in <I>Xenopus</I> Oocytes and Acceleration of Progesterone-Induced G2/M Transition by Oncogenic Forms
Authors: K. Dorey D. Barilá , Gavin A.-C. , Nebreda A.R. , Superti-Furga G. 
Published: September 2004

AbstractDeregulated activity of the Abl protein tyrosine kinase is oncogenic in humans and in animals. The normal cellular form of the enzyme is maintained at a low state of activity by mechanisms that have not yet been entirely elucidated. In particular, little is known about the
Probing Ribosome Structure by Europium-Induced RNA Cleavage
Authors: Dorner S. , Barta A. 
Published: September 2004

AbstractDivalent metal ions are absolutely required for the structure and catalytic activities of ribosomes. They are partly coordinated to highly structured RNA, which therefore possesses high-affinity metal ion binding pockets. As metalion induced RNA cleavages are useful for characterising metal ion binding sites and RNA structures, we analysed europium (Eu3+) induced specific cleavages in both 16S and 23S rRNA ofE. coli. The cleavage sites were identified by primer extension and compared to those previously identified for calcium, lead, magnesium, and manganese ions. Several Eu3+cleavage sites, mostly those at which a general metal ion binding site had been already identified, were identical to previously described divalent metal ions. Overall, the Eu3+cleavages are most similar to the Ca2+cleavage pattern, probably due to a similar ion radius. Interestingly, several cleavage sites which were specific for Eu3+were located in regions implicated in the binding of tRNA and antibiotics. The binding of erythromycin and chloramphenicol, but not tetracycline and streptomycin, significantly reduced Eu3+cleavage efficiencies in the peptidyl transferase center. The identification of specific Eu3+binding sites near the active sites on the ribosome will allow to use the fluorescent properties of europium for probing the environment of metal ion binding pockets at the ribosome's active center.
Conformational Study of the HIV-1 Reverse Transcriptase Inhibitor 1-[(2-Hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT)
Authors: Lawtrakul L. , Hannongbua S. , Beyer A. , Wolschann P. 
Published: September 2004

AbstractThe conformations of the HIV-1 reverse transcriptase inhibitor 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)-thymine (HEPT) are calculated by semiempirical and mainly by
Transient Transfection of Mammary Epithelial Cells with a PEI/DNA/Adenovirus System
Authors: Bischof J. , Vietor I. , Cotten M. , Huber L.A. 
Published: September 2004

Abstract
Studies on epithelial cells often require the transient expression of exogenous proteins in polarized epithelial cells. However, the major limitation of this approach has been the difficulty of obtaining transient gene expression in polarized epithelial cell cultures. We report here on the application of a polyethylenimine (PEI)/DNA/adenovirus system for efficient transient gene expression in mammary epithelial cells. Based on luciferase assay and FACScan analysis the PEI/DNA/adenovirus system is shown to be an effective and simple method for transfecting epithelial cells.
The Core Antigen of Hepatitis B Virus as a Carrier for Immunogenic Peptides
Authors: Murray K. , Shiau A.-L. 
Published: September 2004

AbstractThe core antigen of hepatitis B virus (HBcAg) made inEscherichia coliyields particles that closely resemble the viral nucleocapsid. Extensive modifications can be made to the primary structure of HBcAg without impairing particle assembly. This enables other peptide sequences, including very long sequences, to be added, substituted, or inserted into the nucleocapsid subunit while retaining the ability to form highly immunogenic particles. These also retain the T cell epitopes of HBcAg and constitute powerful delivery systems for a diverse range of immunogenic epitopes and have significant potential for development of multicomponent vaccines.
Enhancing the Immunogenicity of Exogenous Hepatitis B Surface Antigen-Based Vaccines for MHC-I-Restricted T Cells
Authors: Schirmbeck R. , Reimann J. 
Published: September 2004

AbstractVaccination with either exogenous hepatitis B surface antigen (HBsAg) lipoprotein particles without adjuvants, or plasmid DNA encoding secreted small HBsAg stimulate long-lasting, potent antibody responses in H-2d(BALB/c) and C57Bl/6 (H-2b) mice. Vaccination with exogenous HBsAg primes MHC-I restricted cytotoxic T lymphocyte (CTL) responses to HBsAg in H-2dbut not H-2bmice, while DNA vaccination primes HBsAg-specific CTL responses in both mouse strains. We defined vaccination strategies that could elicit CTL responses to exogenous HBsAg in ‘low responder’ C57Bl/6 mice. We found that the bacterial plasmid DNA itself, synthetic oligodeoxynucleotides containing immunostimulating sequences, or recombinant Th1 cytokines (IL12, IFNγ) efficiently support priming of CTL responses to exogenous HBsAg in ‘low responder’ H-2bmice, but have only minor effects on CTL priming in ‘high responder’ H-2dmice in the high dose range tested. These molecularly well defined adjuvants can thus efficiently support priming of anti-viral T cell responses under ‘low responder’ conditions.
Lipopeptides as Dimerization Inhibitors of HIV-1 Protease
Authors: Schramm H. J. , Rosny E. De , Reboud-Ravaux M. , Büttner J. , Dick A. , Schramm W. 
Published: September 2004

AbstractIn AIDS therapy, attempts have been made to inhibit the virus-encoded enzymes, e.g. HIV-1 protease, using active site-directed inhibitors. This approach is questionable, however, due to virus mutations and the high toxicity of the drugs. An alternative method to inhibit the dimeric HIV protease is the targeting of the interface region of the protease subunits in order to prevent subunit dimerization and enzyme activity. This approach should be less prone to inactivation by mutation. A list of improved ‘dimerization inhibitors’ of HIV-1 protease is presented. The main structural features are a short ‘interface’ peptide segment, including non-natural amino acids, and an aliphatic N-terminal blocking group. The high inhibitory power of some of the lipopeptides [e.g. palmitoyl-Tyr-Glu-Leu-OH, palmitoyl-Tyr-Glu-(L-thyronine)-OH, palmitoyl-Tyr-Glu-(L-biphenyl-alanine)-OH] with low nanomolarKivaluesin the enzyme test suggests that mimetics with good bio-availability can be derived for AIDS therapy.