bluuebunny/crossref_metadata_2025_split huggingface dataset:
The risk of central nervous system metastases after trastuzumab therapy in patients with breast carcinoma
Authors: Lai Rose , Dang Chau T. , Malkin Mark G. , Abrey Lauren E. 
Published: June 2004

AbstractBACKGROUNDTrastuzumab, which is a large monoclonal antibody that is efficacious in the treatment of patients with HER‐2/neu‐overexpressing, metastatic breast carcinoma, does not penetrate the blood‐brain barrier and, thus, may allow the brain to become a sanctuary site for micrometastases. Few studies have compared the risk of central nervous system (CNS) metastases in patients treated with or without trastuzumab.METHODSThe authors conducted a retrospective cohort study that compared 264 patients who did not receive trastuzumab therapy with 79 patients who received trastuzumab therapy. The study was powered to detect an effect size of 0.3, which was deemed clinically significant to change future management.RESULTSCNS metastases developed in 48.1% of patients on trastuzumab‐based therapy and in 46.6% of patients on nontrastuzumab‐based therapy. The association between trastuzumab therapy and subsequent CNS metastases (either brain or leptomeningeal) was not significant, with a multivariate‐adjusted odds ratio of 0.91 (95% confidence interval, 0.64–1.88; P = 0.79). Similarly, there was no evidence of an association between trastuzumab and brain metastases alone (P = 0.67) or leptomeningeal metastases alone (P = 0.14). The median overall survival after the diagnosis of all CNS metastases was 26.3 months for patients who did not receive trastuzumab and 24.9 months for patients who received trastuzumab (P = 0.7). A multivariate logistic regression model found that patient age at diagnosis (P < 0.05), positive lymph node status at presentation (P < 0.01), and liver metastases (P < 0.01) were significant predictors of CNS metastases. Lung metastases showed a borderline significant P value (0.056).CONCLUSIONSDespite the impression of many oncologists, the results of this study did not support an association between trastuzumab therapy and an increased risk of CNS metastases. Cancer 2004. © 2004 American Cancer Society.
Embryonic GABAergic spinal commissural neurons project rostrally to mesencephalic targets
Authors: Tran Tracy S. , Cohen‐Cory Susana , Phelps Patricia E. 
Published: June 2004

AbstractAlthough spinal commissural neurons serve as a model system for studying the mechanisms that underlie axonal pathfinding during development, little is known about their synaptic targets. Previously we identified a group of ventromedially located commissural neurons in rat spinal cord that are γ‐aminobutyric acid (GABA)‐ergic and express L1 CAM on their axons. In this study, serial sagittal sections of embryos (E12–15) were processed for glutamic acid decarboxylase (GAD)‐65 and L1 immunocytochemistry and showed labeled commissural axons coursing rostrally within the ventral marginal zone. Both GAD65‐ and L1‐positive axons extended rostrally out of the spinal cord into the central part of the medulla and then into the midbrain. GAD65‐positive axons branched and ended abruptly within the lateral midbrain. To determine the targets of these ventral commissural neurons, embryos (E13–15) were injected with DiI into the ventromedial spinal cord. At all three ages, DiI‐labeled axons projected rostrally in the contralateral ventral marginal zone, turned into the central medulla, and then traveled to the midbrain. DiI‐labeled axons appeared to terminate in the lateral midbrain by branching into small, punctate structures. In reciprocal experiments, DiI injected into the lateral midbrain identified an axon pathway that coursed through the brainstem, into the spinal cord ventral marginal zone, and then filled cell bodies in the contralateral ventromedial spinal cord. A spatial and temporal coincidence was apparent between the GAD65/L1‐ and the DiI‐labeled pathways. Together these findings suggest that some GABAergic commissural neurons are early projection neurons to midbrain targets and most likely represent a spinomesencephalic pathway to the midbrain reticular formation. J. Comp. Neurol. 475:327–339, 2004. © 2004 Wiley‐Liss, Inc.
Superior olivary contributions to auditory system plasticity: Medial but not lateral olivocochlear neurons are the source of cochleotomy‐induced GAP‐43 expression in the ventral cochlear nucleus
Authors: Kraus Kari Suzanne , Illing Robert‐Benjamin 
Published: June 2004

AbstractA unilateral cochlear lesion induces expression of the growth and plasticity‐associated protein 43 (GAP‐43) in fibers and their varicosities on specific types of postsynaptic profiles in the ventral cochlear nucleus (VCN), suggesting the induction of synaptic remodeling. One candidate population from which GAP‐43 might emerge was neurons of the lateral olivocochlear (LOC) system residing in the lateral superior olive (LSO). Upon cochleotomy, these neurons express GAP‐43 mRNA and GAP‐43 protein. However, retrograde axonal tracing with Fast Blue or biotinylated dextran amine from VCN revealed that the number of 6.8 ± 1.3 neurons in the whole ipsilateral LSO labeled in normal adult rats was distinctly small and did not rise after cochleotomy. Concluding that LOC neurons cannot be the source of GAP‐43 in the VCN, we reinvestigated the pattern of GAP‐43 in situ hybridization and found that, after cochleotomy, shell neurons in the regions surrounding the LSO and medial olivocochlear (MOC) neurons in the ventral nucleus of the trapezoid body up‐regulated GAP‐43 mRNA. We then lesioned these regions by means of stereotaxic injections of kainic acid. Destruction of shell neurons preceding an ipsilateral cochleotomy did not change the emergence of GAP‐43 immunoreactivity in the VCN. However, if the contralateral MOC system was lesioned, the rise of GAP‐43 immunoreactivity in VCN on the side of the cochleotomy was significantly reduced. We conclude that, after cochlear dysfunction, MOC neurons are the major (if not exclusive) source of synaptic reorganization in the VCN that could possibly entail compensatory activation of the affected ascending auditory pathway. J. Comp. Neurol. 475:374–390, 2004. © 2004 Wiley‐Liss, Inc.
Fiber connections of the hippocampal formation and septum and subdivisions of the hippocampal formation in the pigeon as revealed by tract tracing and kainic acid lesions
Authors: Atoji Yasuro , Wild J. Martin 
Published: June 2004

AbstractThe organization of the pigeon hippocampal formation was examined by tract tracing by using biotinylated dextran amine (BDA) and cholera toxin B subunit (CTB) and by injections of kainic acid to produce excitotoxic lesions. The hippocampal formation was divided into seven subdivisions based on Nissl staining and intrinsic and septal connections: dorsomedial (DM), dorsolateral (DL), triangular (Tr), V‐shaped layer, magnocellular (Ma), parvocellular, and cell‐poor regions. DL was composed of dorsal and ventral portions and sent associational fibers to DM, the V‐shaped layer, and Tr. DL had strong reciprocal connections with the densocellular part of the hyperpallium (HD) and projected to the dorsolateral corticoid area. DM had reciprocal fiber connections with the V‐shaped layer, Ma, and DL as well as with several subdivisions of the arcopallium. DL and DM, but not the V‐shaped layer, projected fibers to the septum where those from DM exceeded in number those from DL. These projections further extended to the hypothalamus, particularly the lateral hypothalamic area. The lateral and medial septal nuclei projected back a very small number of ascending fibers to the hippocampal formation. Intraventricular injections of kainic acid induced neuronal loss widely in the hippocampal formation and subsequently produced gliosis in DM. These results indicate that DL receives its main afferents from HD and in turn sends inputs to an intrinsic circuit composed of hippocampal subdivisions DM, Ma, Tr, and the V‐shaped layer; and also that DM is the main exit to the septum and hypothalamus. It is suggested that neurons in the V‐shaped layer are intrinsic. Together, the results suggest that the V‐shaped layer is comparable to the dentate gyrus of the mammalian hippocampal formation and that DM incorporates components comparable to both Ammon's horn and the subiculum. J. Comp. Neurol. 475:426–461, 2004. © 2004 Wiley‐Liss, Inc.
Synthesis and Characterization of Platinum(II) Complexes of Diethyl [(Methylsulfinyl)methyl]phosphonate: Potential Drugs against Bone Tumors
Authors: Laforgia Mariarita , Cerasino Leonardo , Margiotta Nicola , Capozzi Maria A. M. , Cardellicchio Cosimo , Naso Francesco , Natile Giovanni 
Published: June 2004

AbstractCisplatin is the most important metal‐based drug used in tumor therapy; however, it suffers from severe side effects and a limited spectrum of activity. Since phosphonates are known to have a selective tropism for bones and calcified tissues, we have carried on the synthesis of different platinum complexes with a phosphonate ligand. The ligand used is diethyl [(methylsulfinyl)methyl]phosphonate (SMP), which can act as an O,S‐donor towards Pt. Moreover, since the sulfur atom is a stable stereogenic center, the ligand is obtained in two enantiomeric forms. The synthesised complexes have the general formula [PtL2(SMP)], in which L2 stands for a bidentate (dimethylmalonate, 1,2‐diaminocyclohexane, ethylenediamine) or two monodentate (chloride) ligands. The formation of a five‐membered chelate ring contributes to the chemical stability of complexes with SMP, and 2D NMR experiments have allowed determination of the ring puckering, which is dependent upon the chirality of the sulfur stereocenter. For the (S) configuration at the sulfur center (free ligand), the δ puckering of the chelate ring is favoured. Preliminary studies have shown that these compounds are stable under physiological conditions. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Long‐term effects of amygdala GABA receptor blockade on specific subpopulations of hippocampal interneurons
Authors: Berretta Sabina , Lange Nicholas , Bhattacharyya Sujoy , Sebro Ronnie , Garces Jessica , Benes Francine M. 
Published: June 2004

AbstractGrowing evidence indicates that the amygdala modulates hippocampal functions. To test the hypothesis that this modulation may involve long‐lasting effects on interneuronal networks in the hippocampus, changes in the expression of neurochemical markers specific for different interneuronal subpopulations were assessed in adult rats 96 h following acute infusion of low doses of the GABAA receptor antagonist picrotoxin into the amygdala. The numerical density (Nd) of somata showing immunoreactivity (IR) for parvalbumin (PVB) was decreased in dentate gyrus (DG) and the CA4–2 region, while that of calretinin (CR)‐IR was decreased in DG and CA2. The Nd of calbindin D28k (CB)‐IR somata was decreased in CA3–2. The densities of axon terminals arising from PVB‐IR and cholecystokinin (CCK)‐IR basket neurons were also altered, with those of CCK‐IR terminals increased across all sectors, while PVB‐IR terminals were decreased only in the CA region. Increases in CCK‐IR terminals were paralleled by increases of terminals with IR for the 65‐kD isoform of glutamate decarboxylase (GAD65). Mixed‐effects statistical models, adapted specifically for these analyses, indicated that perturbations of amygdalar inputs to the hippocampus significantly alter the drive that hippocampal PVB‐, CR‐, and CB‐IR neurons within the dentate gyrus/CA4 region exercise on CCK‐IR terminals within the same region as well as in CA3–1. These results suggest that amygdalar modulation of specific neuronal subpopulations may induce lasting and far‐reaching changes in the hippocampus during normal functioning, as well as in diseases involving a disruption of amygdalar activity. In particular, changes in specific interneuronal markers within selective hippocampal sectors detected in the present results are strikingly similar to those reported in this region in schizophrenia. These similarities suggest that, in this disease, a disruption of GABAergic transmission within the amygdala may play a significant role in the induction of abnormalities in the hippocampus. © 2004 Wiley‐Liss, Inc.
Two New Spermidine Alkaloids from Chisocheton weinlandii
Authors: Tzouros Manuel , Bigler Laurent , Bienz Stefan , Hesse Manfred , Inada Akira , Murata Hiroko , Inatomi Yuka , Nakanishi Tsutomu , Darnaedi Dedy 
Published: June 2004

AbstractThe investigation of the MeOH extract of the leaves of Chisocheton weinlandii Harms (Meliaceae) revealed two new open‐chain spermidine alkaloids, chisitine 1 (1) and chisitine 2 (2). Their structures were elucidated by NMR spectroscopy, tandem‐mass spectrometry, and independant syntheses (Scheme 3). Detailed MS/MS fragmentation pathways are discussed for both compounds based on H/D exchange and 18O‐labeling experiments (Schemes 1 and 2).
Paxillamide: a Novel Phytosphingosine Derivative from the Fruiting Bodies of Paxillus panuoides
Authors: Gao Jin‐Ming , Zhang An‐Ling , Zhang Cun‐Li , Liu Ji‐kai 
Published: June 2004

AbstractThe new phytosphingosine‐type ceramide 1, named paxillamide (=2,3‐dihydroxy‐N‐[(1S,2S,3R)‐2,3‐dihydroxy‐1‐(hydroxymethyl)heptadecyl]tetracosanamide), was isolated from the CHCl3/MeOH extract of the fruiting bodies of the Basidiomycete Paxillus panuoides, and its structure was elucidated by spectroscopic and chemical methods.
Non‐iterative Asymmetric Synthesis of C15 Polyketide Spiroketals
Authors: Meilert Kai , Pettit George R. , Vogel Pierre 
Published: June 2004

AbstractThe 2,2′‐methylenebis[furan] (1) was converted to 1‐{(4R,6S))‐6‐[(2R)‐2,4‐dihydroxybutyl]‐2,2‐dimethyl‐1,3‐dioxan‐4‐yl}‐3‐[(2R,4R)‐tetrahydro‐4,6‐dihydroxy‐2H‐pyran‐2‐yl)propan‐2‐one ((+)‐18) and its (4S)‐epimer (−)‐19 with high stereo‐ and enantioselectivity (Schemes 1–3). Under acidic methanolysis, (+)‐18 yielded a single spiroketal, (3R)‐4‐{(1R,3S,4′R,5R,6′S,7R)‐3′,4′,5′,6′‐tetrahydro‐4′‐hydroxy‐7‐methoxyspiro[2,6‐dioxabicyclo[3.3.1]nonane‐3,2′‐[2H]pyran]‐6′‐yl}butane‐1,3‐diol ((−)‐20), in which both O‐atoms at the spiro center reside in equatorial positions, this being due to the tricyclic nature of (−)‐20 (methyl pyranoside formation). Compound (−)‐19 was converted similarly into the (4′S)‐epimeric tricyclic spiroketal (−)‐21 that also adopts a similar (3S)‐configuration and conformation. Spiroketals (−)‐20, (−)‐21 and analog (−)‐23, i.e., (1R,3S,4′R,5R,6′R)‐3′,4′,5′,6′‐tetrahydro‐6′‐[(2S)‐2‐hydroxybut‐3‐enyl]‐7‐methoxyspiro[2,6‐dioxabicyclo[3.3.1]nonane‐3,2′‐[2H]pyran]‐4′‐ol, derived from (−)‐20, were assayed for their cytotoxicity toward murine P388 lymphocytic leukemia and six human cancer cell lines. Only racemic (±)‐21 showed evidence of cancer‐cell‐growth inhibition (P388, ED50: 6.9 μg/ml).
Windows woes? You may be ready for Linux
Authors: Bean LuAnn , Barlow Judith , Hott David D. 
Published: June 2004

AbstractThey seem to find new security flaws in Microsoft Windows every day. System administrators spend a lot of time downloading and installing software “patches” to fix these problems. Do you have Windows woes? Then you may be ready for a free alternative: the Linux operating system. And it may become popular. Hewlett‐Packard, the number‐one personal computer maker, will begin selling Linux‐based PCs globally. But what are the pros and cons? © 2004 Wiley Periodicals, Inc.
Solvation model induced structural changes in peptides. A quantum chemical study on Ramachandran surfaces and conformers of alanine diamide using the polarizable continuum model
Authors: Hudáky Ilona , Hudáky Péter , Perczel András 
Published: June 2004

AbstractPotential energy surfaces of the model peptide HCO‐L‐Ala‐NH2 were calculated using polarizable continuum model (PCM) for the description of aqueous solution at RHF/3‐21G, RHF/6‐31+G(d), and B3LYP/6‐31+G(d) levels of theory. Energy minima were optimized at all three levels as well as at B3LYP/PCM/6‐311++G(d,p) level of theory. Results were correlated to experimental data of protein structures retrieved from PDB SELECT. It is concluded that alanine residues of proteins are modeled better by PCM results than by gas‐phase calculations on the alanine diamide model (frequently called alanine dipeptide model). The currently available version of the PCM model implemented in Gaussian 03 provides a reasonable alternative to anticipate solvation effects without the computational costs of introducing explicit solvent molecules into the model system. Frequencies calculated at RHF/PCM/6‐31+G(d) and B3LYP/PCM/6‐31+G(d) levels of theory show high correlation; thus, RHF results have their own merit. © 2004 Wiley Periodicals, Inc. J Comput Chem 25: 1522–1531, 2004
Cell‐cycle control and the cartilage growth plate
Authors: Beier Frank 
Published: June 2004

AbstractThe longitudinal growth of endochondral bones is governed by proliferation and hypertrophic differentiation of growth plate chondrocytes. Numerous growth factors and hormones have been implicated in the regulation of these processes, but the intracellular mechanisms involved remain much less understood. We had suggested a role of cell‐cycle genes in the integration of these diverse extracellular signals and their translation into coordinated proliferation and differentiation of chondrocytes. Numerous recent studies have provided support for such a scenario and provide novel insights into the regulation and function of cell‐cycle genes in chondrocytes. This review article summarizes recent progress in the field. © 2005 Wiley‐Liss, Inc.
Patterns of spatial and temporal visceral arch muscle development in the Mexican axolotl (Ambystoma mexicanum)
Authors: Ericsson Rolf , Olsson Lennart 
Published: June 2004

AbstractVertebrate head development is a classical topic that has received renewed attention during the last decade. Most reports use one of a few model organisms (chicken, mouse, zebrafish) and have focused on molecular mechanisms and the role of the neural crest, while cranial muscle development has received less attention. Here we describe cranial muscle differentiation and morphogenesis in the Mexican axolotl, Ambystoma mexicanum. To determine the onset of differentiation we use antibodies against desmin and optical sectioning using confocal laser scanning microscopy on whole‐mount immunostained embryos. This technique makes it possible to document the cranial muscle in three dimensions while keeping the specimens intact. Desmin expression starts almost simultaneously in the first, second, and third visceral arch muscles (as in other amphibians studied). Muscle anlagen divide up early into the different elements which constitute the larval cranial musculature. We extend and refine earlier findings, e.g., by documenting a clear division between interhyoideus and interhyoideus posterior. The timing of cranial muscle differentiation differs among vertebrate groups, but seems to be constant within each group. This study provides a morphological foundation for further studies of muscle cell fate and early differentiation. J. Morphol. 261:131–140, 2004. © 2004 Wiley‐Liss, Inc.
Development of the nasal chemosensory organs in two terrestrial anurans: The directly developing frog, Eleutherodactylus coqui (Anura: Leptodactylidae), and the metamorphosing toad, Bufo americanus (Anura: Bufonidae)
Authors: Jermakowicz Walter J. , Dorsey David A. , Brown Amy L. , Wojciechowski Karen , Giscombe Claudette L. , Graves Brent M. , Summers Cliff H. , Ten Eyck Gary R. 
Published: June 2004

AbstractNearly all vertebrates possess an olfactory organ but the vomeronasal organ is a synapomorphy for tetrapods. Nevertheless, it has been lost in several groups of tetrapods, including aquatic and marine animals. The present study examines the development of the olfactory and vomeronasal organs in two terrestrial anurans that exhibit different developmental modes. This study compares the development of the olfactory and vomeronasal organs in metamorphic anurans that exhibit an aquatic larva (Bufo americanus) and directly developing anurans that have eliminated the tadpole (Eleutherodactylus coqui). The olfactory epithelium in larval B. americanus is divided into dorsal and ventral branches in the rostral and mid‐nasal regions. The larval olfactory pattern in E. coqui has been eliminated. Ontogeny of the olfactory system in E. coqui embryos starts to vary substantially from the larval pattern around the time of operculum development, the temporal period when the larval stage is hypothesized to have been eliminated. The nasal anatomy of the two frogs does not appear morphologically similar until the late stages of embryogenesis in E. coqui and the terminal portion of metamorphosis in B. americanus. Both species and their respective developing offspring, aquatic tadpoles and terrestrial egg/embryos, possess a vomeronasal organ. The vomeronasal organ develops at mid‐embryogenesis in E. coqui and during the middle of the larval period in B. americanus, which is relatively late for neobatrachians. Development of the vomeronasal organ in both frogs is linked to the developmental pattern of the olfactory system. This study supports the hypothesis that the most recent common ancestor of tetrapods possessed a vomeronasal organ and was aquatic, and that the vomeronasal organ was retained in the Amphibia, but lost in some other groups of tetrapods, including aquatic and marine animals. J Morphol. 261:225–248, 2004. © 2004 Wiley‐Liss, Inc.
Dynamics of HIV replication in lymphocytes and the efficacy of protease inhibitors
Authors: Bermejo Mercedes , Sánchez‐Palomino Sonsoles , Usán Luis , Alcamí José 
Published: June 2004

AbstractUsing a system that allows transfection of resting peripheral blood lymphocytes (PBLs) two questions were addressed: the kinetics of HIV replication from the state of proviral latency, and the impact of different parameters on the efficacy of protease inhibitors to control HIV replication. PBLs were transfected with an infectious full length HIV‐DNA harboring a luciferase reporter gene and activated thereafter. Ritonavir was added at different times at doses ranging from to 0.06 to 1 μM. Viral expression was assessed by quantifying luciferase activity in cell extracts and levels of p24 HIV antigen in culture supernatants. After transfection and cell activation, intracellular expression of HIV proteins, as assessed by luciferase detection, occurred within 2 hr. HIV‐gag p24 antigen was detected in culture supernatants between 6 and 8 hr post‐activation. Ritonavir was effective in blocking viral replication when given within 4 hr following HIV reactivation, but a delay in ritonavir administration or breaches in ritonavir levels after 6 hr from transfection resulted in viral escape. HIV reactivation from proviral latency in PBLs is an extremely rapid process, faster than estimated from previous models. These data stress the need for maintaining effective antiretroviral concentrations to block completely viral replication. J. Med. Virol. 73:502–507, 2004. © 2004 Wiley‐Liss, Inc.