bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Phase II study of paclitaxel by 24‐hour infusion and ifosfamide in anthracycline‐resistant metastatic breast carcinoma
Authors: Seo Jae H. , Whang Young M. , Kim Byung S. , Choi Chul W. , Shin Sang W. , Kim Yeul H. , Kim Jun S. , Goo Bum H. 
Published: August 2002

AbstractBACKGROUNDA Phase II study was performed to investigate the efficacy and tolerability of paclitaxel and ifosfamide chemotherapy for the treatment of anthracycline‐resistant metastatic breast carcinoma (MBC).METHODSRecurrent or progressed MBC within 12 months after anthracycline‐based chemotherapy was defined as anthracycline‐resistant. A 24‐hour infusion of paclitaxel (175 mg/m2) on Day 1 and subsequent infusions of ifosfamide (1.8 g/m2/day) with mesna (360 mg/m2/day) on Days 2– 4, were performed every 3 weeks. Twenty‐one patients were eligible for toxicity analysis. Response rate and survival duration were evaluated in 21 patients. Frontline chemotherapy was the FAC (5‐fluorouracil, doxorubicin, cyclophosphamide) regimen in all patients.RESULTSObjective response was found in 9 patients (42.9%), including complete response in 3 (13.4%). Median response duration and median survival duration were 10 months (range, 2–24+) and 19+ months (range, 2–32+), respectively. Sixteen (76%) experienced Grade 3/4 leukopenia controllable with granulocyte macrophage colony‐stimulating factor. Other significant toxicities were peripheral neuropathy (n = 3), mucositis (n = 2), and liver dysfunction (n = 1). However, there was no chemotherapy‐related death.CONCLUSIONSPaclitaxel by 24‐hour infusion combined with ifosfamide is efficacious in the treatment of anthracycline‐resistant MBC with tolerable toxicity. Further trials verifying the result of the authors' study are warranted. Cancer 2002;94:1925–30. © 2002 American Cancer Society.DOI 10.1002/cncr.10431
The dynamics of prostate specific antigen during watchful waiting of prostate carcinoma
Authors: Vollmer Robin T. , Egawa Shin , Kuwao Sadahito , Baba Shiro 
Published: August 2002

AbstractBACKGROUNDFor the moment, there is uncertainty about the usefulness of early treatment of localized prostate carcinoma, uncertainty about whether some patients with early cancer can be managed expectantly, and uncertainty about how such patients might be recognized.METHODSThe authors studied serial values of prostate specific antigen (PSA) in 94 Japanese men with diagnosed prostate carcinoma and who were managed by watchful waiting. Their median follow‐up duration was 32 months (range, 1.6–118). The authors used a log‐linear model to fit the values of PSA over time, and then they used the Cox survival model to relate the intercept (PSA amplitude) and slope (relative velocity) to observed local or systemic outcomes that were independent of PSA.RESULTSThe authors found that the log‐linear model fit the serial values of PSA during watchful waiting very well. Prostate specific antigen amplitude related significantly to T classification (P = 0.0006), but not to grade (P > 0.2), and the relative velocity related significantly to both T classification (P = 0.009) and to grade (P = 0.02). Although the T classification, histologic grade, and log(PSA) at diagnosis were associated significantly with time to outcome, the combination of amplitude and relative velocity provided more information. These 2 PSA parameters resulted in a higher model likelihood ratio, and their individual P values in the Cox model were 0.0005 and 0.005, respectively. With these two in the Cox model, T classification, grade, log(PSA), and PSA doubling time provided no further significant information.CONCLUSIONSA log‐linear model seems to fit serial measurements of PSA during watchful waiting, and preliminary results suggest that both the amplitude and the relative velocity relate closely to clinical outcomes. Cancer 2002;94:1692–8. © 2002 American Cancer Society.DOI 10.1002/cncr.10443
Topoisomerase IIα gene expression is regulated by the p53 tumor suppressor gene in nonsmall cell lung carcinoma patients
Authors: Liu Dage , Huang Cheng‐long , Kameyama Kotaro , Hayashi Eiichi , Yamauchi Akira , Sumitomo Shinichi , Yokomise Hiroyasu 
Published: August 2002

AbstractBACKGROUNDTopoisomerase IIα (Topo IIα) is an essential nuclear enzyme for chromosome segregation during mitosis. Previous experimental studies using cell lines reported that Topo IIα expression was negatively regulated by wild‐type p53 through the gene's promoter region.METHODSSurgically resected tumor specimens from 98 nonsmall cell lung carcinoma (NSCLC) patients who were not treated with preoperative chemotherapy were studied. Quantitative reverse‐transcription polymerase chain reaction analysis was done to evaluate Topo IIα gene expression. Polymerase chain reaction single strand conformation polymorphism following sequencing was performed to investigate mutations of p53.RESULTSTopo IIα gene expression in squamous cell carcinomas was significantly higher than in adenocarcinomas (P = 0.0007). Topo IIα gene expression in moderately differentiated tumors and poorly differentiated tumors was significantly higher than in well differentiated tumors (P = 0.0032 and P = 0.0005, respectively). Thirty nine tumors (40%) had mutations of p53. Topo IIα gene expression in tumors with mutant p53 was significantly higher than in those with wild‐type p53 (P = 0.0224).CONCLUSIONSThe current study suggests that Topo IIα gene expression is regulated by p53 gene status in NSCLC patients and that the overexpression of Topo IIα induced by mutant p53 might cause more aggressive carcinogenesis. Cancer 2002;94:2239–47. © 2002 American Cancer Society.DOI 10.1002/cncr.10450
Prognostic value of cyclin B1 in patients with esophageal squamous cell carcinoma
Authors: Takeno Shinsuke , Noguchi Tsuyoshi , Kikuchi Ryuichi , Uchida Yuzo , Yokoyama Shigeo , Müller Wolfram 
Published: August 2002

AbstractBACKGROUNDIt has been reported that p53 regulates the G2‐M checkpoint transition through cyclin B1, and it has been suggested that p53 plays an important role in the development and progression of various malignancies. The objective of the current study was to clarify the role of the cell cycle regulators, cyclin B1 and p53, in patients with esophageal squamous cell carcinoma (ESCC).METHODSTissue samples from 71 patients with ESCC were included in the current study. Expression levels of cyclin B1 and p53 in samples of normal squamous epithelium, dysplasia, and tumor cells from patients with ESCC were analyzed by immunohistochemistry.RESULTSSeveral cells in the basement layer of normal epithelium expressed cyclin B1. The number of cyclin B1 positive cells tended to increase as the degree of dysplasia increased from low grade to high grade. More than 20% of tumor cells were cyclin B1 positive in 38 patients (49.3%). Several clinicopathologic parameters, including macroscopic configuration (P < 0.01), pathologic tumor status (P < 0.05), pathologic lymph node status (P < 0.001), pathologic metastatic status (P < 0.01), tumor stage (P < 0.0001), and invasion of lymphatic vessels (P < 0.05), were correlated with the overexpression of cyclin B1. Elevated expression levels of cyclin B1 also were correlated with a poor prognosis in patients with ESCC in univariate analysis (P < 0.0001) and multivariate analysis (P = 0.0135). In contrast, p53 expression exhibited no significant correlation with the level of cyclin B1 expression and was not associated with prognostic parameters in patients with ESCC.CONCLUSIONSThese findings suggest that cyclin B1 is involved in the pathogenesis of carcinoma of the esophagus and that elevated levels of cyclin B1 expression, but not p53 expression, may indicate a poor prognosis for patients with ESCC. Cancer 2002;94:2874–81. © 2002 American Cancer Society.DOI 10.1002/cncr.10542
Hypophysiotropic neurons of the paraventricular nucleus respond in spatially, temporally, and phenotypically differentiated manners to acute vs. repeated restraint stress: Rapid publication
Authors: Viau Victor , Sawchenko Paul E. 
Published: August 2002

AbstractHypothalamic‐pituitary‐adrenal (HPA) responses to stress are initiated by parvicellular neurosecretory neurons in the medial parvicellular (mp) part of the paraventricular hypothalamic nucleus (PVH), which express corticotropin‐releasing factor (CRF), among other neuropeptides. We have used an approach guided by patterns of stress‐induced Fos expression to explore the manner in which anatomically and phenotypically defined components of the mpPVH respond to acute vs. repeated restraint stress. Hormonal indices of HPA activation in animals exposed to the last of 14 daily repeated restraint sessions were significantly lower than those in rats receiving a single restraint episode. Although this habituation was paralleled by global decrements in activation patterns across all PVH compartments, clear spatial‐temporal differences in recruitment profiles were noted between dorsal and ventral aspects of the mpPVH. Thus, acute restraint provoked a biphasic Fos induction, which occurred first within the mpPVH and in an adjoining population of somatostatinergic cells in the periventricular region and only later within other aspects of the PVH. By contrast, Fos responses of habituated animals were monophasic and focused decisively within a discrete ventral aspect of the mpPVH. The ventral population was identified as comprising neurons that express CRF and/or enkephalin and, to a lesser extent, growth hormone‐releasing factor. These results indicate a lack of homogeneity among stress‐responsive parvicellular neurosecretory neurons and suggest that distinct complements of CRF cells may be preferentially involved in initiating HPA responses to acute stress and sustaining them in the repeated condition. J. Comp. Neurol. 445:293–307, 2002. © 2002 Wiley‐Liss, Inc.
Parkin immunoreactivity in the brain of human and non‐human primates: An immunohistochemical analysis in normal conditions and in Parkinsonian syndromes
Authors: Zarate‐Lagunes Martin , Gu Wen‐Jie , Blanchard Véronique , Francois Chantal , Muriel Marie‐Paule , Mouatt‐Prigent Annick , Bonici Bruno , Parent André , Hartmann Andreas , Yelnik Jérôme , Boehme Georg A. , Pradier Laurent , Moussaoui Saliha , Faucheux Baptiste , Raisman‐Vozari Rita , Agid Yves , Brice Alexis , Hirsch Etienne C. 
Published: August 2002

AbstractThe etiology of Parkinson's disease is unknown, but the gene involved in an autosomic recessive form of the disease with early onset has recently been identified. It codes for a protein with an unknown function called parkin. In the present study we produced a specific polyclonal antiserum against human parkin. Immunohistochemical analysis showed that parkin is expressed in neuronal perikarya and processes but also in glial and blood vessels in the primate brain (human and monkey). Electron microscopy indicated that parkin immunoreactivity is mostly located in large cytoplasmic vesicles and at the level of the endoplasmic reticulum. Parkin was expressed heterogeneously in various structures of the brain. It was detectable in the dopaminergic systems at the level of the perikarya in the mesencephalon but also in the striatum. However, parkin was also expressed by numerous nondopaminergic neurons. The staining intensity of parkin was particularly high in the hippocampal formation, the pallidal complex, the red nucleus, and the cerebellum. Comparison of control subjects with patients with Parkinson's disease and control animals with 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐intoxicated animals revealed a loss of parkin‐immunoreactive neurons only in the substantia nigra pars compacta. Furthermore, the surviving dopaminergic neurons in the parkinsonian state continued to express parkin at a level similar to that observed in the control situation. These data indicate that parkin is a widely expressed protein. Thus, the degeneration of dopaminergic neurons in familial cases of Parkinson's disease with autosomal recessive transmission cannot be explained solely in terms of an alteration of this protein. J. Comp. Neurol. 432:184–196, 2001. © 2001 Wiley‐Liss, Inc.
Topographic organization of suprachiasmatic nucleus projection neurons
Authors: Leak Rehana K. , Moore Robert Y. 
Published: August 2002

AbstractThe mammalian circadian pacemaker, the hypothalamic suprachiasmatic nucleus (SCN), has two subdivisions. The core is located above the optic chiasm, receives primary and secondary visual afferents, and contains neurons producing vasoactive intestinal polypeptide and gastrin‐releasing peptide. The shell largely surrounds the core, receives input from nonvisual sources and contains neurons producing arginine vasopressin and calretinin. In this study, we tested the hypothesis that SCN efferent projections are topographically organized with respect to the subdivision of origin. Injections of retrograde tracers were placed in major sites of efferent termination, described from prior studies that used anterograde tracers (Watts and Swanson, [1987] J. Comp. Neurol. 258:230–252; Watts et al. [1987] J. Comp. Neurol. 258:204–229). After retrograde tracer injections in the medial preoptic area, dorsomedial and paraventricular hypothalamic nuclei, bed nucleus of stria terminalis, paraventricular thalamic nucleus, zona incerta, and medial subparaventricular zone, retrogradely labeled SCN cells are clustered in the shell with few labeled neurons in the core. After injections centered in the lateral subparaventricular zone, peri‐suprachiasmatic region, lateral septum, or ventral tuberal area, the majority of neuronal label is in the core with moderate to sparse neuronal label in the shell. Both subdivisions are labeled after injections in the paratenial thalamic nucleus. The same pattern of retrograde labeling is found with four tracers, cholera toxin‐β subunit, Fluoro‐Gold, the Bartha strain of pseudorabies virus, and biotinylated dextran amine. These data extend our understanding of the significance of the division of the SCN into shell and core by demonstrating that the subdivisions differ in the pattern of projections. Together with prior observations that the subdivisions differ with respect to afferents, local connections, and neuroactive substances, the present study provides an anatomic basis for discrete control of circadian function by the SCN core and shell. In this novel view, the nature of the signal conveyed to areas receiving core or shell projections varies as a function of the subdivision from which innervation is derived. J. Comp. Neurol. 433:312–334, 2001. © 2001 Wiley‐Liss, Inc.
Pattern of expression of engrailed in relation to gamma‐aminobutyric acid immunoreactivity in the central nervous system of the adult grasshopper
Authors: Siegler Melody V.S. , Pankhaniya Ravi R. , Jia Xi Xi 
Published: August 2002

AbstractEngrailed (En) protein expression in neurons of the mesothoracic and metathoracic ganglia of the adult grasshopper, Schistocerca americana, was examined by immunohistochemistry. Each neuromere had a dorsally located cluster of En‐positive neurons within the dorsal unpaired median (DUM) group, comprising one cluster in the mesothoracic ganglion (T2) and four clusters in the metathoracic ganglion, one for each component neuromere (T3, A1, A2, A3). Ventrally, En‐positive neurons occurred in the posterior one‐third of each neuromere. In T2 and T3, three ventral groups of neurons were labeled bilaterally. In the abdominal neuromeres, many fewer ventral neurons were En‐positive. These also were bilaterally symmetrical, but did not occur in patterns that allowed assignment of homology with the T2 and T3 groups. Altogether, En‐positive neurons comprised roughly 10% of the ganglionic populations. In the bilateral groups, as in the DUM groups, En expression was restricted to interneurons, consistent with the suggestion that En expression contributes to some aspect of interneuronal phenotype. En‐positive neurons in the DUM groups also expressed gamma‐aminobutyric acid (GABA) immunoreactivity. Further study showed that all neurons in one En‐positive bilateral group and some neurons in another bilateral group were GABA immunoreactive, but that neurons in a third bilateral group were En‐positive only. Additionally, several discrete clusters of neurons were GABA‐immunoreactive but En‐negative. A provisional morphological scheme is presented, which relates the several neuronal clusters to their likely neuroblasts of origin, as a basis for further research into the composition of neuronal lineages. J. Comp. Neurol. 440:85–96, 2001. © 2001 Wiley‐Liss, Inc.
Axon collaterals of meynert cells diverge over large portions of area V1 in the macaque monkey
Authors: Rockland Kathleen S. , Knutson Tina 
Published: August 2002

AbstractPatchy intrinsic connections, originating mainly from horizontal collaterals of pyramidal neurons, have been demonstrated in area V1 and many other cortical areas. In this article, we identify a network of intrinsic connections concentrated in layer 6 of area V1. These are visualized by extracellular injections of anterograde tracers in V1, which label small clusters of large terminal boutons in layer 6, in conjunction with thick axon segments. These segments can be traced back to infragranular Meynert cells (n = 10), which are retrogradely labeled from the injections. By using serial section analysis, we identified the following features of this distinctive system of Meynert cell collaterals: (1) terminal clusters are relatively small (<100 μm); (2) each cluster has a small number of rather large boutons (up to 3.0 μm); (3) there is typically a termination‐free zone in the immediate vicinity (0.5–2.0 mm) of the cell body; (4) a single neuron has multiple branches that can extend up to 8.0 mm from the soma; and (5) the collaterals are concentrated in layer 6. These features are different from those of horizontal intrinsic connections in the supragranular layers of area V1. They are consistent with fast dynamics and a possible role in wide‐field motion processing, such as has been associated with Meynert cells from other studies. J. Comp. Neurol. 441:134–147, 2001. © 2001 Wiley‐Liss, Inc.
Dye exclusion artifact in flow cytometers
Authors: Steen Harald B. , Stokke Trond 
Published: August 2002

AbstractBackgroundCells exclude their own volume of dye solution in the sample flow which carries them through the flow chamber of the flow cytometer, thereby affecting the otherwise constant signal arising from the fluorescence of this solution. Under certain conditions, this phenomenon may significantly influence the fluorescence signal of the cells.Materials and MethodsUsing the slit scan technique, we studied this phenomenon as observed for monodisperse polystyrene particles in fluorescein solution.ResultsThe measurements show that dye solution accumulates just in front of the particle and just behind it, with a relative void in between. This phenomenon is most likely caused by the rapid constriction of the flow as it enters the orifice of the nozzle or flow chamber, giving rise to a pulse of fluorescence which adds to that of the particle or cell itself. The magnitude of this artifact depends on the design and dimensions of the nozzle/flow chamber as well as on the rate of sample flow.ConclusionsThe dye exclusion artifact may affect measurements of cells when they are in a dye solution having a fluorescence per unit volume which is significant compared to that of the cells, especially at low sample flow rates. Cytometry 47:200–205, 2002. © 2002 Wiley‐Liss, Inc.
Mitochondrial and nonmitochondrial reduction of MTT: Interaction of MTT with TMRE, JC‐1, and NAO mitochondrial fluorescent probes
Authors: Bernas Tytus , Dobrucki Jurek 
Published: August 2002

AbstractBackgroundBioreduction of water‐soluble tetrazolium salts (e.g., MTS, XTT, and MTT) to their respective formazans is generally regarded as an indicator of cell “redox activity.” The reaction is attributed mainly to mitochondrial enzymes and electron carriers. However, MTT reduction may also be catalyzed by a number of other nonmitochondrial enzymes. The goal of this work was to establish the sites of MTT reduction in intact HepG2 human hepatoma cells in culture.MethodsIn order to establish the subcellular localization of the sites of reduction of MTT, we imaged the formation of MTT‐formazan deposits using backscattered light confocal microscopy. Mitochondria were visualized in viable cells using fluorescent dyes that bind in a manner dependent (JC‐1 and TMRE) or independent (NAO) of mitochondrial electric potential.ResultsOnly 25–45% of MTT‐formazan was associated with mitochondria after 25 min of incubation. No more than 25% of the mitochondrial area on images was occupied by MTT‐formazan. Mitochondrial fluorescence of TMRE, NAO, and the monomeric form of JC‐1 decreased rapidly in cells incubated with MTT. However, the intensity of fluorescence of JC‐1 aggregates dropped by less than 30% at the onset of incubation and remained constant as reduction of MTT proceeded further.Conclusions(1) Most of MTT‐formazan deposits are not coincident with mitochondria. (2) Monomeric JC‐1, as well as TMRE and NAO, accumulating in mitochondria may be displaced by MTT. Thus, the presence of positively charged organic compounds (like MTT) may distort measurements of mitochondrial transmembrane electric potential, which are based on accumulation of fluorescent dyes. Cytometry 47:236–242, 2002. © 2002 Wiley‐Liss, Inc.
Comparison between different laboratory tests for the detection and prevention of heparin‐induced thrombocytopenia
Authors: Vitale Marco , Tazzari Pierluigi , Ricci Francesca , Mazza Maria Anna , Zauli Giorgio , Martini Giuliana , Caimi Luigi , Manzoli Francesco A. , Conte Roberto 
Published: August 2002

AbstractBackground: Heparin‐induced thrombocytopenia (HIT) is a possible complication of heparin therapy that can evolve with life‐threatening thromboembolism, for which early diagnosis is essential. However, the specific laboratory approach to the diagnosis of HIT is still controversial. Methods: Sera from 13 patients with HIT, from 15 patients with non‐HIT thrombocytopenia, and from 10 normal subjects were used to compare nonfunctional and functional methods to detect anti‐heparin:PF‐4 antibodies and platelet activation. We used three enzyme‐linked immunosorbent assays (ELISAs) and the particle gel immunoassay as nonfunctional tests, and platelet aggregometry, CD62p (p‐selectin) phenotypical expression, and Annexin V binding as functional assays. Results: CD62p expression was positive in 85% of the cases and Annexin V was positive in 40% of the HIT cases examined. Aggregometry gave variable results that depend strongly on the donor. Conclusion: Functional tests for platelet activation are more reliable for HIT diagnosis than the nonfunctional tests. We conclude that the phenotypical expression of p‐selectin detected by flow cytometry on activated platelets appears to be a good functional marker for the diagnosis of HIT and its possible thromboembolic complications. Cytometry (Comm. Clin. Cytometry) 46:290–295, 2001. © 2001 Wiley‐Liss, Inc.
Advances in optical networking
Authors: Papadimitriou G. I. , Obaidat M. S. , Pomportsis A. S. 
Published: August 2002

AbstractAn overview of optical networks is provided. An introduction into the area of optical networks, their abilities and characteristics and their place in today's communication technology are made. The various components that an optical network consists of are examined. These include examination of the structure and operation of optical fibres, optical transmitters and receivers, optical amplifiers and other related optical components. The various classes of optical networks—optical link networks, broadcast and select networks, wavelength‐routed networks, photonic packet‐switching networks and optical burst switching ones—are then explained. Finally, an examination of various trends in the optical networking area is made. Copyright © 2001 John Wiley & Sons, Ltd.