bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II study of neoadjuvant 1, 3‐bis (2‐chloroethyl)‐1‐nitrosourea and temozolomide for newly diagnosed anaplastic glioma
Authors: Chang Susan M. , Prados Michael D. , Yung W. K. Alfred , Fine Howard , Junck Larry , Greenberg Harry , Robins H. Ian , Mehta Minesh , Fink Karen L. , Jaeckle Kurt A. , Kuhn John , Hess Kenneth , Schold Clifford 
Published: March 2004

AbstractBACKGROUNDTemozolomide (TMZ) and 1, 3‐bis (2‐chloroethyl)‐1‐nitrosourea (BCNU) are reported to be active agents in anaplastic glioma (AG). TMZ has also been shown to deplete alkyltransferase, a DNA repair enzyme that contributes to nitrosourea resistance. The objective of the current study was to determine the efficacy and toxicity profile of a combination of these agents before radiotherapy in newly diagnosed AG.METHODSEligibility criteria included histologically confirmed newly diagnosed AG with measurable enhancing disease, a Karnofsky performance score (KPS) ≥ 60, normal pulmonary function, and normal laboratory parameters. In addition, informed consent was obtained from all patients. BCNU given at a dose of 150 mg/m2 intravenously was followed after 2 hours by TMZ given at a dose of 550 mg/m2 orally on Day 1 of a 42‐day cycle to a maximum of 4 cycles, unless there was tumor progression or unacceptable toxicity.RESULTSForty‐one eligible patients were accrued. Their median age was 40 years. Seventy‐six percent of patients had a KPS of 90–100. The histology was 81% anaplastic astrocytoma, 12% anaplastic oligodendroglioma, and 7% mixed tumors. Twenty‐two percent of patients did not complete 4 cycles because of toxicity, mainly hematologic. Forty‐six percent of patients experienced Grade 3 or 4 (according to National Cancer Institute Common Toxicity Criteria) thrombocytopenia. Twenty percent had Grade 4 granulocytopenia. Two patients died while receiving therapy, 1 of progressive disease and the other of Pneumocystis carinii pneumonia. The complete and partial response rates were 2% and 27% respectively. An additional 54% of patients had stable disease. Seventeen percent developed progressive disease (10% after the first cycle and 7% after the second cycle).CONCLUSIONSThis neoadjuvant strategy was associated with significant myelosuppression and a modest response rate in patients with newly diagnosed AG. Cancer 2004. © 2004 American Cancer Society.
Cancer screening and the periodic health examination
Authors: Smith Robert A. , Wender Richard C. 
Published: March 2004

In this issue of Cancer, Chen et al. report outcomes from an integrated model of multiphasic chronic disease screening in Taiwan. The design and outcomes of the Keelung Community‐based Integrated Screening program are noteworthy for several reasons and should reopen the debate not only regarding the worth, but also the protocol for periodic preventive health examinations.See also pages 000–000.
Community‐based multiple screening model
Authors: Chen Tony Hsiu‐Hsi , Chiu Yueh‐Hsia , Luh Dih‐Ling , Yen Ming‐Fang , Wu Hui‐Min , Chen Li‐Sheng , Tung Tao‐Hsin , Huang Chih‐Chung , Chan Chang‐Chuan , Shiu Ming‐Neng , Yeh Yen‐Po , Liou Horng‐Huei , Liao Chao‐Sheng , Lai Hsin‐Chih , Chiang Chun‐Pin , Peng Hui‐Ling , Tseng Chuen‐Den , Yen Ming‐Shyen , Hsu Wei‐Chih , Chen Chih‐Hung 
Published: March 2004

AbstractBACKGROUNDMultiple disease screening may have several advantages over single disease screening because of the economics of scale, with the high yield of detecting asymptomatic diseases, the identification of multiple diseases or risk factors simultaneously, the enhancement of the attendance rate, and the efficiency of follow‐up.METHODSAn integrated model of community‐based multiple screening was designed and conducted between 1999 and 2001 in Keelung, Taiwan. The authors used a Papanicolaou (Pap) smear screening program as a base to integrate other screening regimens encompassing four other neoplastic diseases and three nonneoplastic chronic diseases. Screening methods, the interscreening interval, and the follow‐up for each screening regimen were designed based on evidence‐based literature and current national screening policy.RESULTSA total of 42,387 subjects participated in the screening activities. A 25% increase in the attendance rate for Pap smear screening was demonstrated after the introduction of multiple disease screening programs. At the first screen, this program yielded a total of 677 asymptomatic neoplasms (16.0 per 1000), including a large proportion of precancerous lesions and small presymptomatic tumors without lymph node involvement. The association between the occurrence of neoplasm and the presence of comorbid nonneoplastic chronic disease was found to be statistically significant (odds ratio, 1.64; 95% confidence interval, 1.38–1.94 [P < 0.05]). The authors also identified 5314 subjects with metabolic syndrome who were at a greater risk for colorectal and oral neoplasias.CONCLUSIONSThe results of the current study demonstrate that an outreach and community‐based multiple screening program not only enhances attendance rates but also has a high yield of early cases of various diseases simultaneously, and provides a natural opportunity to elucidate the correlation between neoplastic disease and nonneoplastic chronic disease. Cancer 2004. © 2004 American Cancer Society.
Memory and a priori best strategy in complex adaptive systems
Authors: Quito Marcelino , Monterola Christopher , Saloma Caesar 
Published: March 2004

AbstractWe employ an agent‐based model to show that memory and the absence of an a priori best strategy are sufficient for self‐segregation and clustering to emerge in a complex adaptive system with discrete agents that do not compete over a limited resource nor contend in a winner‐take‐all scenario. An agent starts from a corner of a two‐dimensional lattice and aims to reach a randomly selected site in the opposite side within the shortest possible time. The agent is isolated during the course of its journey and does not interact with other agents. Time‐bound obstacles appear at random lattice locations and the agent must decide whether to challenge or evade any obstacle blocking its path. The agent is capable of adapting a strategy in dealing with an obstacle. We analyze the dependence of strategy‐retention time with strategy for both memory‐based and memory‐less agents. We derive the equality spectrum to establish the environmental conditions that favor the existence of an a priori best strategy. We found that memory‐less agents do not polarize into two opposite strategy‐retention time distributions nor cluster toward a center distribution. © 2004 Wiley Periodicals, Inc. Complexity 9: 41–46, 2004
Automated microscopy identifies estrogen receptor subdomains with large‐scale chromatin structure unfolding activity
Authors: Carpenter Anne E. , Ashouri Anousheh , Belmont Andrew S. 
Published: March 2004

AbstractBackgroundRecently, several transcription factors were found to possess large‐scale chromatin unfolding activity; these include the VP16 acidic activation domain, BRCA1, E2F1, p53, and the glucocorticoid and estrogen steroid receptors. In these studies, proteins were fluorescently labeled and targeted to a multimerized array of DNA sequences in mammalian cultured cells, and changes in the appearance and/or size of the array were observed. This type of experiment is impeded by the low throughput of traditional microscopy.MethodsWe report the application of automated microscopy to provide unattended, rapid, quantitative measurements of fluorescently labeled chromosome regions.ResultsThe automated image collection routine produced results comparable to results previously obtained by manual methods and was significantly faster. Using this approach, we identified two subdomains within the E domain of estrogen receptor α capable of inducing large‐scale chromatin decondensation.ConclusionsThis work confirms that, like BRCA1, the activation function 2 region of the estrogen receptor has more than one distinct chromatin unfolding domain. In addition, we demonstrate the feasibility of using automated microscopy as a high‐throughput screen for identifying modulators of large‐scale chromatin folding. The Supplementary Material referred to in this article can be found at the CYTO Part A website (http://www.interscience.wiley.com/jpages/0196‐4763/suppmat/v58A.html) © 2004 Wiley‐Liss, Inc.
Suppression of photobleaching‐induced artifacts in frequency‐domain FLIM by permutation of the recording order
Authors: van Munster Erik B. , Gadella Theodorus W.J. 
Published: March 2004

AbstractBackgroundPhotobleaching can lead to significant errors in frequency‐domain fluorescence lifetime imaging microscopy (FLIM). Existing correction methods for photobleaching require additional recordings and processing time and can result in additional noise. A method is introduced that suppresses the effects of photobleaching without the need for extra recordings or processing.MethodsExisting bleach correction methods and the method introduced in this report whereby the recording order of the phases is permuted were compared using numerical simulations.ResultsCertain orders were found to make measurements virtually insensitive to photobleaching. At 12 recordings, errors in measured phase and modulation depth decreased by a factor 512 and 393, respectively, compared to recordings using sequential recording order. The optimal order is independent of modulation depth, phase, and extent of photobleaching. Thus, the same order can be used for practically all situations. Application of the method in FLIM measurements of EYFP‐transfected HeLa cells was found effectively to suppress photobleaching induced artifacts.ConclusionsIn view of the ease of implementation, its inherent robustness, and the possibility to still apply existing correction methods afterward, there is no good reason not to use the permuted recording order presented in this report instead of a sequential order. © 2004 Wiley‐Liss, Inc.
Assessment of histone H2AX phosphorylation induced by DNA topoisomerase I and II inhibitors topotecan and mitoxantrone and by the DNA cross‐linking agent cisplatin
Authors: Huang Xuan , Okafuji Masaki , Traganos Frank , Luther Ed , Holden Elena , Darzynkiewicz Zbigniew 
Published: March 2004

AbstractBackgroundDNA double‐strand breaks (DSBs) in chromatin, whether induced by radiation, antitumor drugs, or by apoptosis‐associated (AA) DNA fragmentation, provide a signal for histone H2AX phosphorylation on Ser‐139; the phosphorylated H2AX is denoted γH2AX. The intensity of immunofluorescence (IF) of γH2AX was reported to reveal the frequency of DSBs in chromatin induced by radiation or by DNA topoisomerase I (topo 1) and II (topo 2) inhibitors. The purpose of this study was to further characterize the drug‐induced (DI) IF of γH2AX, and in particular to distinguish it from AA γH2AX IF triggered by DNA breaks that occur in the course of AA DNA fragmentation.MethodsHL‐60 cells in cultures were treated with topotecan (TPT), mitoxantrone (MTX), or with DNA cross‐linking drug cisplatin (CP); using multiparameter flow and laser‐scanning cytometry, induction of γH2AX was correlated with: 1) caspase‐3 activation; 2) chromatin condensation, 3) cell cycle phase, and 4) AA DNA fragmentation. The intensity of γH2AX IF was compensated for by an increase in histone/DNA content, which doubles during the cell cycle, and for the “programmed” H2AX phosphorylation, which occurs in untreated cells.ResultsIn cells treated with TPT or MTX, the increase in DI‐γH2AX IF peaked at 1.5 or 2 h, and was maximal in S‐ or G1‐phase cells, respectively, for each drug. In cells treated with CP, compared with TPT, the γH2AX IF was less intense, peaked later (3 h) and showed no cell cycle–phase specificity. In the presence of phosphatase inhibitor calyculin A, a continuous increase in the TPT‐induced γH2AX IF was still seen past 1.5 h, and after 3 h γH2AX IF was 2.7‐ to 3.4‐fold higher than in the absence of the inhibitor. The AA γH2AX IF was distinguished from the DI‐γH2AX IF by: 1) its greater intensity; 2) its prevention by caspase inhibitor zVAD‐FMK; and 3) the concurrent activation of caspase‐3 in the same cells. A decrease in AA γH2AX IF coinciding with AA chromatin condensation was seen in the late stages of apoptosis.ConclusionsMultiparameter analysis of γH2AX IF, caspase‐3 activation, cellular DNA content, and chromatin condensation allowed us to distinguish the DI from AA H2AX phosphorylation and relate them to the cell cycle phase and stage of apoptosis. With a comparable degree of ds DNA breaks, the cells arrested at the G1 or G2/M checkpoint were less prone to undergo apoptosis than the cells replicating DNA. H2AX phosphorylation seen in CP‐treated cells may be associated with DNA repair that involves nucleotide excision repair (NER) and nonhomologous end joining (NHEJ). When the primary drug‐induced lesions do not involve ds DNA breaks, but ds DNA breaks are formed during DNA repair, as in the case of CP, analysis of H2AX phosphorylation may reflect extent of the repair process. © 2004 Wiley‐Liss, Inc.
Design and validation of a tool for neurite tracing and analysis in fluorescence microscopy images
Authors: Meijering E. , Jacob M. , Sarria J.‐C.F. , Steiner P. , Hirling H. , Unser M. 
Published: March 2004

AbstractBackgroundFor the investigation of the molecular mechanisms involved in neurite outgrowth and differentiation, accurate and reproducible segmentation and quantification of neuronal processes are a prerequisite. To facilitate this task, we developed a semiautomatic neurite tracing technique. This article describes the design and validation of the technique.MethodsThe technique was compared to fully manual delineation. Four observers repeatedly traced selected neurites in 20 fluorescence microscopy images of cells in culture, using both methods. Accuracy and reproducibility were determined by comparing the tracings to high‐resolution reference tracings, using two error measures. Labor intensiveness was measured in numbers of mouse clicks required. The significance of the results was determined by a Student t‐test and by analysis of variance.ResultsBoth methods slightly underestimated the true neurite length, but the differences were not unanimously significant. The average deviation from the true neurite centerline was a factor 2.6 smaller with the developed technique compared to fully manual tracing. Intraobserver variability in the respective measures was reduced by a factor 6.0 and 23.2. Interobserver variability was reduced by a factor 2.4 and 8.8, respectively, and labor intensiveness by a factor 3.3.ConclusionsProviding similar accuracy in measuring neurite length, significantly improved accuracy in neurite centerline extraction, and significantly improved reproducibility and reduced labor intensiveness, the developed technique may replace fully manual tracing methods. © 2004 Wiley‐Liss, Inc.
Emergence of long‐term memory for conditioned aversion in the rat fetus
Authors: Gruest Nadège , Richer Paulette , Hars Bernard 
Published: March 2004

AbstractPregnant rats were subjected to garlic essential oil as the conditioned stimulus and 45 min later to LiCl as the unconditioned stimulus either on embryonic Days 15 and 16 (E15 and E16) or on 18 and 19 (E18 and E19). Control dams received only garlic, LiCl, or water. Progenies were tested on garlic drinking 6 weeks after the exposure to the stimuli via the mothers. In the E18 to 19 group, rats that were exposed to paired garlic–LiCl expressed a significant aversion for garlic. In the E15 to 16 group, no significant differences appeared between subgroups. These results confirm that an associative memory can be established before birth and suggests that this ability potentially emerges in a short time window of 3 days at the end of gestation. Moreover, it appears that a long‐term memory can be acquired in utero and retained to be expressed postnatally when animals are autonomous. © 2004 Wiley Periodicals, Inc. Dev Psychobiol 44: 189–198, 2004.
Hyperinsulinemic hypoglycemia of infancy: the challenge continues
Authors: Dekelbab Bassem H. , Sperling Mark A. 
Published: March 2004

AbstractHypoglycemia due to hyperinsulinemia is the most common cause of persistent hypoglycemia in infants and children. Recent discoveries in the molecular and biochemical regulation of insulin secretion have dramatically increased our understanding of the disorders responsible for syndromes of hyperinsulinemic hypoglycemia. Here, we briefly review the current knowledge of disorders of the KATP channel, activating mutations of glucokinase and glutamate dehydrogenase (GDH) and other disorders that may be associated with specific phenotypes and permit appropriate targeted therapies. Despite these advances, much remains to be learned. We do not understand the mechanisms or defects in many instances, including defective carbohydrate glycosylation syndromes and perinatal hypoxia, both of which may be associated with hyperinsulinemia. Most importantly, preoperative distinction between diffuse and focal lesions cannot be always reliably made even after selective arterial infusion with calcium, glucose or a sulfonylurea with concurrent hepatic venous sampling for insulin. The ability to distinguish diffuse from localized lesions has profound implications for therapeutic approaches, prognosis and genetic counseling. To date, about 50% of individuals with hyperinsulinemic hypoglycemia of infancy can be correctly categorized. Thus, the challenge continues. Copyright © 2004 John Wiley & Sons, Ltd.
Peroxidase activity in the intestinal tract of Wistar–Furth, BBc and BBdp rats
Authors: Courtois Philippe , Sener Abdullah , Scott Fraser W. , Malaisse Willy J. 
Published: March 2004

AbstractBackgroundThe development of immune‐mediated diabetes in BB rats may involve an inflammatory lesion of the intestinal tract.MethodsIn order to further explore this issue, the activity of peroxidase was measured, in the absence and presence of either bromide or dapsone, at day 10, 30, 45, 70, 95 and 120 in three segments (top, mid and bottom) of the intestinal tract from Wistar–Furth rats and both diabetes‐resistant and diabetes‐prone BB rats fed after weaning either diabetes‐promoting diets or a protective diet, which decreases the incidence of diabetes in the BB rats.ResultsIn the present study, from day 30 onwards, an age‐related increase in peroxidase activity was found in the intestine of diabetes‐prone BB rats (BBdp rats) fed diabetogenic diets, when compared with either Wistar–Furth or diabetes‐resistant BB rats (BBc rats). This increase was most pronounced in the distal segments of the intestinal tract. Even when fed a protective diet, higher peroxidase activity was found in BBdp than BBc rats. Yet, in BBc rats, and to a lesser extent in BBdp rats, the diabetogenic diets lowered peroxidase activity below the value found in rats of the same strain fed the protective diet. There was a tight correlation between the activity of peroxidase and its susceptibility to be increased by bromide.ConclusionIt is proposed that diabetogenic diets may decrease peroxidase activity in intestinal cells, this effect becoming masked in BBdp rats by an age‐related increase in the contribution of inflammatory cells. The latter phenomenon affects preferentially the distal segments of the intestinal tract. Copyright © 2004 John Wiley & Sons, Ltd.
Linear Multinuclear RuII Photosensitizers
Authors: Vaduvescu Simona , Potvin Pierre G. 
Published: March 2004

AbstractFour ditopic bridging ligands, containing 2,2′:6′,2′′‐terpyridine and 2,6‐dipyrazinylpyridine (dpp) metal‐binding units attached through p‐ or m‐phenylene linkages, have been incorporated into eight mono‐, di‐ and trinuclear linear RuII complexes. These were characterized by UV/Vis spectroscopy and cyclic voltammetry, and by their ability to undergo light‐induced electron transfers to methylviologen. The dpp‐bearing complexes were more difficult to prepare but were superior sensitizers, a fact attributable to longer excited state lifetimes and an electrostatically favored reductive quenching pathway. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Electrochemical Studies of Complexes with Oxo‐ or Hydroxo‐Bridged {Mo2(µ‐SMe)3}+ Centers: Cleavage of the Oxygen Bridge and Generation of Substrate‐Binding Sites
Authors: Le Hénanf Marc , Le Roy Christine , Muir Kenneth W. , Pétillon François Y. , Schollhammer Philippe , Talarmin Jean 
Published: March 2004

AbstractThe reduction of [Mo2(Cp)2(µ‐SMe)3(µ‐O)]+ (1+) has been investigated by cyclic voltammetry and controlled‐potential electrolysis in THF‐ and MeCN/NBu4PF6 without added acid or in the presence of various acids HX (HX: HTsO, CF3CO2H, HBF4). Reduction in the presence of acid follows an ECrevE mechanism in which the intermediate chemical step is an acid‐base equilibrium between 1 and [Mo2(Cp)2(µ‐SMe)3(µ‐OH)]+ (2+). This electrochemical process is followed by protonation of the neutral µ‐hydroxo complex 2 to afford different products which depend both on the solvent (THF or MeCN) and on the nature of the acid. Controlled‐potential electrolysis of 1+ in the presence of HX (2 equiv.) leads to the generation of binding sites and finally gives products identical to those obtained from protonation of 2 by HX. The complex [Mo2(Cp)2(µ‐SMe)3(µ‐η1,η1‐OCOCF3)] (3) which can be obtained either by protonation of 2 by CF3CO2H or by reduction of 1+ in the presence of CF3CO2H, has been characterized crystallographically. In the presence of HBF4 protonation of 1+ gives 22+. The reactivity of 2+ and of the complexes [Mo2(Cp)2(µ‐SMe)3(H2O)(TsO)] (4) and [Mo2(cp)2(µ‐SMe)3(H2O)L]+ (L = H2O or THF) (6+), all of which contain a terminal aqua ligand, has also been investigated. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Catalysis at the Interface of Ruthenium Carbene and Ruthenium Hydride Chemistry: Organometallic Aspects and Applications to Organic Synthesis
Authors: Schmidt Bernd 
Published: March 2004

AbstractSoon after the introduction of stable and defined ruthenium precatalysts for olefin metathesis it was discovered that double bond migrations may interfere with the metathesis reaction. This undesired side reaction has been attributed to the formation of ruthenium hydride species from metathesis‐active ruthenium carbene species in situ. Over the past few years, several studies have indeed revealed the existence of pathways leading from ruthenium carbene to ruthenium hydride complexes. Furthermore, a number of examples have been published recently where typical precatalysts for olefin metathesis were found to promote non‐metathesis transformations efficiently in preparatively useful yields and selectivities, presumably via the in situ formation of ruthenium hydride species. These results open up a pathway to the development of novel catalyzed reaction sequences that combine ruthenium carbene‐ and ruthenium‐hydride‐mediated steps. This paper provides an overview of the field and covers organometallic aspects as well as synthetic applications. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Solvation Effect of Li+ on the Voltammetric Properties of [PMo12O40]3−. Part 2: Comparative Studies on the Preferential Solvation in Acetonitrile+S and Acetone+S Mixtures
Authors: Himeno Sadayuki , Takamoto Masayo , Ueda Tadaharu , Santo Ryoko , Ichimura Akio 
Published: March 2004

AbstractFor [PMo12O40]3−, the presence of Li+ produced a two‐electron wave at nearly the same potential as the first one‐electron wave in acetonitrile or acetone. The voltammetric behavior of [PMo12O40]3− in a binary mixture of acetonitrile and solvent S was compared with those in a mixture of acetone and S. When the donor number (DN) of S>20, the first two‐electron wave was converted into one‐electron waves in such binary mixtures. The conversion occurred at lower mole fractions of S in an acetonitrile+S mixture than in an acetone+S mixture. The 7Li NMR results showed that the preferential solvating ability of Li+ with S was greater in the former mixture. A linear relationship was found between the iso‐solvation point xiso(S) and the reciprocal of the difference between the DNs of S and acetonitrile, which gave the basis to explain the anomalies observed for a mixture of acetonitrile and H2O.