bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prostate carcinoma tissue proteomics for biomarker discovery
Authors: Zheng Yaxin , Xu Ye , Ye Bin , Lei Junyi , Weinstein Michael H. , O'Leary Michael P. , Richie Jerome P. , Mok Samuel C. , Liu Brian C.‐S. 
Published: December 2003

AbstractBACKGROUNDThe advent of the prostate‐specific antigen (PSA) test has had a profound impact on the diagnosis and treatment of prostate carcinoma. However, the use of PSA levels alone for screening for prostate carcinoma was compromised by the variations in the amount of PSA produced by the benign prostatic tissue specimens. Proteins were involved in various pathways that determine the behavior of a cell. Therefore, information regarding proteins may reveal drug targets and/or markers for early detection.METHODSThe authors used surface‐enhanced laser desorption/ionization time‐of‐flight mass spectrometry to determine the protein profiles from fresh tissues of the prostate. Laser capture microdissection was performed to isolate pure populations of cells.RESULTSThe authors identified a protein with an average m/Z of 24,782.56 ± 107.27 that was correlated with the presence of prostate carcinoma. Furthermore, using laser capture microdissection, they demonstrated that the origin of this protein, which the authors designated PCa‐24, was derived from the epithelial cells of the prostate. PCa‐24 expression was detected in 16 of 17 (94%) prostate carcinoma specimens but not in paired normal cells. In addition, this protein was not expressed in any of the 12 benign prostatic hyperplasia specimens that were assayed.CONCLUSIONSPCa‐24 may be useful a marker for prostate carcinoma. Cancer 2003;98:2576–82. © 2003 American Cancer Society.
Alemtuzumab as treatment for residual disease after chemotherapy in patients with chronic lymphocytic leukemia
Authors: O'Brien Susan M. , Kantarjian Hagop M. , Thomas Deborah A. , Cortes Jorge , Giles Francis J. , Wierda William G. , Koller Charles A. , Ferrajoli Alessandra , Browning Mary , Lerner Susan , Albitar Maher , Keating Michael J. 
Published: December 2003

AbstractBACKGROUNDThe objective of this study was to investigate the efficacy and safety of alemtuzumab, the humanized anti‐CD52 monoclonal antibody, in patients with B‐cell chronic lymphocytic leukemia and residual disease after chemotherapy.METHODSForty‐one patients received alemtuzumab 3 times weekly for 4 weeks. The first 24 patients received 10 mg per dose, and the next 17 patients received 30 mg. All patients received infection prophylaxis during therapy and for 2 months after treatment.RESULTSThe overall response rate was 46%, including 39% of patients who received the 10 mg dose and responded versus 56% of the patients who received the 30 mg dose. The major reason for failure to respond was the presence of adenopathy. Residual bone marrow disease cleared in most patients, and 11 of 29 patients (38%) achieved a molecular disease remission. The median time to disease progression had not been reached in responders with a median follow‐up of 18 months. Six patients remained in disease remission between 24–38 months after therapy. Infusion‐related events were common with the initial doses, but all such events were NCI Common Toxicity Criteria Grade 1–2. Infections were reported to occur in 15 patients (37%), and 9 of these infections were reactivation of cytomegalovirus. Three patients developed Epstein–Barr virus positive, large cell lymphoma. Two patients had spontaneous resolution of the lymphoma and, in one patient, the lymphoma resolved after treatment with cidofovir and immunoglobulin.CONCLUSIONSAlemtuzumab produced significant responses in patients with residual disease after chemotherapy. Bone marrow disease was eradicated more frequently than lymph node disease, and molecular disease remissions were achieved. A randomized trial comparing alemtuzumab with observation after chemotherapy is indicated. Cancer 2003;98:2657–63. © 2003 American Cancer Society.
Imatinib mesylate in Philadelphia chromosome‐positive leukemia of childhood
Authors: Kolb E. Anders , Pan Qiulu , Ladanyi Marc , Steinherz Peter G. 
Published: December 2003

AbstractBACKGROUNDInitial treatment for adult patients with Philadelphia chromosome‐positive (Ph[+]) chronic myelogenous leukemia (CML) now includes imatinib mesylate. However, to our knowledge, there are few data regarding imatinib safety, efficacy, and response monitoring in patients age < 18 years.METHODSIn the current series, the authors report 5 consecutive patients ages 20 months to 12 years with Ph(+) leukemia who were treated with imatinib and evaluated for a response using cytogenetics, fluorescent in situ hybridization (FISH), and real‐time quantitative reverse transcriptase–polymerase chain reaction (RT‐PCR) on serial bone marrow aspirations. Doses of imatinib were escalated as tolerated from a starting dose of 400 mg/m2 (patients with a body surface area [BSA] < 1 m2) or 400 mg/day (patients with a BSA > 1 m2).RESULTSAfter the initiation of imatinib therapy, all 4 patients with CML were found to have no detectable Ph chromosome by cytogenetics (median of 198 days of imatinib therapy; range, 138–346 days), FISH (median of 285 days of imatinib therapy; range, 138–366 days), and real‐time RT‐PCR (median of 287 days of imatinib therapy; range, 224–366 days). One patient with Ph(+) acute mixed lineage leukemia achieved a morphologic disease remission with standard chemotherapy, but within 10 months had increasing Ph positivity in consecutive bone marrow aspirations. Imatinib was added to the intensive leukemia therapy, and within 26 days there were no detectable Ph(+) cells in the bone marrow. Mild thrombocytopenia was noted in two patients and transient mild hepatic toxicity was noted in one patient.CONCLUSIONSImatinib mesylate was found to be effective in inducing undetectable residual disease in a small cohort of pediatric patients with Ph(+) leukemia. Further studies of the use of imatinib in childhood Ph(+) malignancies are needed. Cancer 2003;98:2643–50. © 2003 American Cancer Society.
The US's retreat from the Kyoto Protocol: an account of a policy change and its implications for future climate policy
Authors: Steurer Reinhard 
Published: December 2003

AbstractIn March 2001, President G.W. Bush announced that the United States had abandoned the ratification of the Kyoto Protocol. This paper describes the historical background as well as the political reasons and mechanisms behind the Bush administration's decision. Moreover, it deals with two alternative policy proposals, which have emerged at the US federal and the state level since then. The paper then highlights some important differences between EU and US climate change policies. The most important difference is that the EU wants global warming mitigation and the US, if necessary at all, is emphasizing the need to adapt to climate change. The paper concludes by suggesting that if a post‐Kyoto treaty wants to bring the US back on board it will need to address this difference. Copyright © 2003 John Wiley & Sons, Ltd and ERP Environment.
An adaptive virtual topology reconfiguration policy in multi‐wavelength optical Internet
Authors: Lee Kyunghee , Zhang Lin , Youn Chan‐Hyun 
Published: December 2003

AbstractThis paper studies the issues arising in the virtual topology reconfiguration phase of optical Internet networks. This reconfiguration process means to change a virtual topology in response to the changing traffic patterns in a higher layer. We formulate the optimal reconfiguration policy as a multi‐stage decision‐making problem to maximize the expected reward and cost function over an infinite horizon. To counter the continual approximation problem brought by heuristic approach, we take the traffic prediction into consideration. We further propose a new heuristic reconfiguration scheme called prediction based multi‐stage reconfiguration approach to realize the optimal reconfiguration policy based on predicted traffic. Simulation results show that our reconfiguration policy significantly outperforms the conventional one, while the required physical resources are limited. Copyright © 2003 AEI.
Disruption of the genomic imprint in trans with homologous recombination at Snrpn in ES cells
Authors: Tsai Ting‐Fen , Bressler Jan , Jiang Yong‐hui , Beaudet Arthur L. 
Published: December 2003

AbstractSummary: In gene targeting studies of the Prader‐Willi syndrome (PWS)/Angelman syndrome (AS) domain in mouse ES cells, we recovered only recombinants with the paternal allele for constructs at exons 2 or 3 of the imprinted, maternally silenced Snurf‐Snrpn gene. These sites lie close to the imprinting center (IC) for this domain. In contrast, recombinants for Ube3a within the same imprinted domain were recovered with equal frequency on the maternal and paternal alleles. In addition, gene targeting of the paternal allele for Snurf‐Snrpn resulted in partial or complete demethylation in trans with activation of expression for the previously silenced maternal allele. The imprint switching of the maternal allele in trans is not readily explained by competition for trans‐acting factors and adds to a growing body of evidence indicating homologous association of oppositely imprinted chromatin domains in somatic mammalian cells. genesis 37:151–161, 2003. © 2003 Wiley‐Liss, Inc.
Generation of a germ cell nuclear factor conditional allele in mice
Authors: Lan Zi‐Jian , Xu Xueping , Cooney Austin J. 
Published: December 2003

AbstractSummary: Two recombination steps in embryonic stem (ES) cells were adopted to generate a floxed Germ Cell Nuclear Factor (GCNF) allele. First, a targeting vector containing a loxP site upstream of exon 4, encoding the DNA binding domain (DBD), and a floxed NeoTK double selection cassette downstream of exon 4 was integrated into the GCNF locus by homologous recombination. Second, a Cre‐expressing vector was transiently introduced to remove the floxed NeoTK cassette via site‐specific recombination. Heterogeneous ES cell populations were found in a single colony after Cre transfection and were separated using an ES cell re‐pick step. Floxed GCNF mice were generated and had normal GCNF expression in the adult gonads. Using the Msx2Cre transgenic mice, the floxed GCNF can be completely deleted in the female germline. Taken together, the floxed GCNF mice were successfully generated and female germline deletion of the floxed GCNF allele was achieved using Msx2Cre mice. genesis 37:172–179, 2003. © 2003 Wiley‐Liss, Inc.
Electroporation of cynomolgus monkey embryonic stem cells
Authors: Furuya Masataka , Yasuchika Kentaro , Mizutani Ken‐ichi , Yoshimura Yasunori , Nakatsuji Norio , Suemori Hirofumi 
Published: December 2003

AbstractEfficient genetic modification of primate embryonic stem (ES) cells is essential for the application for both basic and preclinical research. The transfection efficiency of primate ES cells is reportedly lower than that of mouse ES cells. Cynomolgus monkey ES cells provide a powerful model for understanding human development and disease. We evaluated electroporation as a method to introduce foreign genes into cynomolgus monkey ES cells. Our examination has allowed us to establish a protocol producing about 100 stably transfected clones from 107 cynomolgus monkey ES cells. Differences in efficiency, however, were observed for other ES cell lines. We compared the transcriptional activities of the PGK‐1, CMV, and SV40 promoters in cynomolgus monkey ES cells generating efficient G418 selection. Although the PGK‐1 and SV40 promoters efficiently drove neo gene expression, the CMV promoter was significantly less transcriptionally active in cynomolgus monkey ES cells. Using this electroporation method, we established fluorescent cynomolgus monkey ES cell lines. These cells may be useful tools for tracing grafted cells in transplantation studies using a variety of functional cells derived from cynomolgus monkey ES cells. genesis 37:180–187, 2003. © 2003 Wiley‐Liss, Inc.
Dlx5/6‐enhancer directed expression of Cre recombinase in the pharyngeal arches and brain
Authors: Ruest Louis‐Bruno , Hammer Robert E. , Yanagisawa Masashi , Clouthier David E. 
Published: December 2003

AbstractDlx5 and Dlx6, two members of the Distalless gene family, are required for development of numerous tissues during embryogenesis, including facial and limb development. This gene pair is expressed in tandem, transcribed toward each other and separated by a short intergenic region containing multiple putative enhancers. Targeted inactivation of Dlx5 and Dlx6 in mice results in multiple developmental defects in craniofacial and limb structures, suggesting that these genes are crucial for aspects of both neural crest and nonneural crest development. To further investigate potential developmental roles of Dlx5 and Dlx6, we used one of the Dlx5/6 intergenic enhancers to drive Cre recombinase expression in transgenic mice. Crossing Dlx5/6‐Cre transgenic mice with mice from the R26R strain results in β‐galactosidase staining in the apical ectodermal ridge, brain, and neural crest‐derived mesenchyme of the pharyngeal arches, with staining in term embryos observed in the facial skeleton and specific brain structures. However, in contrast to endogenous expression patterns of Dlx5 and Dlx6, Cre expression within the pharyngeal arches occurs during a very narrow window in early development. Our studies suggest that Dlx5/6‐Cre mice may prove useful both in further understanding the function and regulation of Distalless genes during development and in studies of gene function in conditional knockout mice. genesis 37:188–194, 2003. © 2003 Wiley‐Liss, Inc.
Neuropsychological correlates of hippocampal and rhinal cortex volumes in patients with mesial temporal sclerosis
Authors: O'Brien Catherine E. , Bowden Stephen C. , Bardenhagen Fiona J. , Cook Mark J. 
Published: December 2003

AbstractConsiderable progress has been made toward understanding the function of the primate rhinal cortex, comprising the entorhinal (ErC) and perirhinal (PrC) cortices. However, translating animal models to human memory has been limited by the technological problems associated with characterizing neural structures in vivo. Functional correlates of hippocampal and rhinal cortex volume changes were examined in a sample of 61 temporal lobe epilepsy patients with mesial temporal sclerosis (MTS; 33 left, 28 right). Patients were administered the Wechsler Adult Intelligence Scale (revised or third edition), the Wechsler Memory Scale (revised or third edition), and a spatial maze task. Neuropsychological data, together with rhinal cortex and hippocampal volumes, collected in our earlier study (O'Brien CE, Bowden SC, Whelan G, Cook MJ, unpublished observations), were analyzed using multiple regression. The only significant predictor of verbal memory function was the difference score between the volume of left hippocampus and the left PrC. Spatial maze scores were predicted by the bilateral sum of ErC volume. The difference score between the left hippocampus and left PrC volumes was the most powerful predictor of verbal episodic memory. Right hippocampal volume was not a significant predictor of nonverbal episodic memory. Verbal and nonverbal semantic memory were not significantly predicted by any combination of rhinal cortex structures. This quantitative study suggests a lateralized or material‐specific memory function for the left hippocampus and left PrC, in contrast to the bilateral role of the ErC. The left hippocampus and left PrC appear to act on verbal memory function through an opposing relationship. Finally, differentiation between hippocampal and subhippocampal components in terms of episodic and semantic memory, respectively, could not be supported by the current data. © 2003 Wiley‐Liss, Inc.
Conduction latency along CA3 hippocampal axons from rat
Authors: Soleng Anne F. , Raastad Morten , Andersen Per 
Published: December 2003

AbstractRelatively few physiological studies have been carried out on intrahippocampal axons. We have recorded compound potentials from fiber groups and the activity of individual axons at 22–25°C to characterize the conduction in subsets of the broad fan‐shaped CA3 pyramidal axonal tree, including the Schaffer collaterals and longitudinal branches. The same wide axonal branching was indicated by antidromic activation of individual CA3 pyramidal cells. The average compound action potential latency from the CA3 to the CA1 area (Schaffer collaterals) increased by 4.16 ± 0.06 ms/mm separation between the stimulation and registration electrodes. The impulses spread 31% faster in the 45‐degree oblique temporal than in the transverse direction across CA1. The latency of the longitudinal axons in the CA3 area increased by 6.19 ± 0.19 ms/mm. More impressive than these direction‐dependent differences in latency were the large differences between individual axons running in the same direction. For both the longitudinal axons and the Schaffer collaterals, there was a broad distribution of antidromic latencies for a given distance between the stimulation and recording points. Typically, the fastest impulses arrived in half the time of the slowest. The distribution of compound action potential latencies between two points in the tissue could be made narrower by surgical restriction of the thickness and width of the preparation. By comparison, the cerebellar parallel fibers showed a narrower distribution of their latencies than the Schaffer collaterals. Because the cerebellar fibers run more straight than Schaffer collaterals, this suggested that some of the latency differences of the latter were due to differences in the path length of the axons. One consequence of our findings is that synchronous firing of neighboring CA3 pyramidal cells does not necessarily give synchronous inputs to common target CA1 neurons. © 2003 Wiley‐Liss, Inc.
Morphological and numerical analysis of synaptic interactions between neurons in deep and superficial layers of the entorhinal cortex of the rat
Authors: van Haeften Theo , Baks‐te‐Bulte Luciënne , Goede Peter H. , Wouterlood Floris G. , Witter Menno P. 
Published: December 2003

AbstractNeurons providing connections between the deep and superficial layers of the entorhinal cortex (EC) constitute a pivotal link in the network underlying reverberation and gating of neuronal activity in the entorhinal‐hippocampal system. To learn more of these deep‐to‐superficial neurons and their targets, we applied the tracer Neurobiotin™ pericellularly in layer V of the medial EC of 12 rats. Labeled axons in the superficial layers were studied with light and electron microscopy, and their synaptic organization recorded. Neurobiotin‐labeled layer V neurons displayed “Golgi‐like” staining. Two major cell types were distinguished among these neurons: (1) pyramidal neurons with apical spiny dendrites traversing all layers and ramifying in layer I, and (2) horizontal neurons with dendrites confined to the deep layers. Labeled axons ramified profusely in layer III, superficially in layer II and deep in layer I. Analysis of labeled axon terminals in layers I–II and III showed that most synapses (95%) were asymmetrical. Of these synapses, 56% occurred with spines (presumably belonging to principal neurons) and 44% with dendritic shafts (presumably interneurons). A small fraction of the synapses (5%) was of the symmetrical type. Such synapses were mainly seen on dendritic shafts. We found in two sections a symmetrical synapse on a spine. These findings suggest that the deep to superficial projection is mainly excitatory in nature, and that these fibers subserve both excitation and feed‐forward inhibition. There is an additional, much weaker, inhibitory component in this projection, which may have a disinhibitory effect on the entorhinal network in the superficial layers. © 2003 Wiley‐Liss, Inc.
Differential neuronal fates in the CA1 hippocampus after hypoxia in newborn and 7‐day‐old rats: Effects of pre‐treatment with MK‐801
Authors: Grojean Stéphanie , Pourié Grégory , Vert Paul , Daval Jean‐Luc 
Published: December 2003

AbstractThe brain displays an age‐dependent sensitivity to ischemic insults. However, the consequences of oxygen deprivation per se in the developing brain remain unclear, and the role of glutamate excitotoxicity via N‐methyl‐D‐aspartate (NMDA) receptors is controversial. To gain a better understanding of the mechanisms involved in the cerebral response to severe hypoxia, cell damage was temporally monitored in the CA1 hippocampus of rat pups transiently exposed to in vivo hypoxia (100% N2) at either 24 h or 7 days of age. Also, the influence of a pre‐treatment with the NMDA receptor antagonist MK‐801 (5 mg/kg, i.p.) was examined. At both ages, morphometric analyses and cell counts showed hypoxia‐induced significant neuronal loss (30–35%) in the pyramidal layer, with injury appearing more rapidly in rats exposed at 7 days. Morphological alterations of 4,6‐diamidino‐2‐phenylindole (DAPI)‐labeled nuclei, DNA fragmentation patterns on agarose gels, as well as expression profiles of the apoptosis‐related regulatory proteins Bax and Bcl‐2 showed that apoptosis was prevalent in younger animals, whereas only necrosis was detected in hippocampi of rats treated at 7 days. Moreover, pre‐treatment with MK‐801 was ineffective in protecting hippocampal neurons from hypoxic injury in newborn rats, but significantly reduced necrosis in older subjects. These data confirm that hypoxia alone may trigger neuronal death in vivo, and the type of cell death is strongly influenced by the degree of brain maturity. Finally, NMDA receptors are not involved in the apoptotic consequences of hypoxia in the newborn rat brain, but they were found to mediate necrosis at 7 days of age. © 2003 Wiley‐Liss, Inc.