bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular genetic alterations in the laser‐capture–microdissected stroma adjacent to bladder carcinoma
Authors: Paterson Ryan F. , Ulbright Thomas M. , MacLennan Gregory T. , Zhang Shaobo , Pan Chong‐Xian , Sweeney Christopher J. , Moore Curtiss R. , Foster Richard S. , Koch Michael O. , Eble John N. , Cheng Liang 
Published: October 2003

AbstractBACKGROUNDUrothelial carcinoma commonly manifested loss of heterozygosity (LOH) at different regions of chromosomes 17p, 3p, and 9q. Recent studies suggested that bladder stromal cells may be implicated in the growth and progression of urothelial carcinoma. To better understand the genetic alterations in the stromal cells in patients with bladder carcinoma, the authors evaluated the prevalence of allelic loss at three microsatellite polymorphic markers on chromosomes 17p13 (TP53), 3p25‐26 (D3S3050), and 9q32‐33 (D9S177). In addition, the pattern of X‐chromosome inactivation of the stromal cells was evaluated by analyzing the DNA methylation pattern at a polymorphic site on the androgen receptor gene.METHODSThe authors studied 18 female patients who underwent either transurethral resection (n = 2) or radical cystectomy (n = 16) for high‐grade muscle‐invasive urothelial carcinoma of the urinary bladder. Genomic DNA samples from the stromal cells immediately adjacent to the tumor and the tumor itself were prepared from formalin‐fixed, paraffin‐processed tissues using laser‐assisted microdissection and LOH was determined.RESULTSThe stromal cells showed a high frequency of LOH on chromosomes 17p13 (29%), 3p25‐26 (61%), and 9q32‐33 (47%) with no clear concordance with the adjacent tumor cells. Fourteen specimens (78%) showed LOH in the stroma in at least 1 of 3 markers examined. Nonrandom X‐chromosome inactivation was frequent in the stromal cells (50% of informative specimens).CONCLUSIONSThe current study revealed that some of the genetic changes that commonly occur with invasive urothelial carcinoma were frequently found in the adjacent stroma and suggested that the stroma of urothelial carcinoma may play an important role in bladder carcinogenesis. Cancer 2003. © 2003 American Cancer Society.
A neurocomputational model for prostate carcinoma detection
Authors: Kalra Pankaj , Togami Joanna , Bansal B.S. Gaurav , Partin Alan W. , Brawer Michael K. , Babaian Richard J. , Ross Lawrence S. , Niederberger Craig S. 
Published: October 2003

AbstractBACKGROUNDCurrent guidelines for prostate carcinoma screening rely primarily on the digital rectal examination (DRE) and prostate specific antigen (PSA). Well described patient risk factors for prostate carcinoma also include age, ethnicity, family history, and complexed PSA. However, due to the nonlinear relation of each of these variables with prostate carcinoma, it is difficult to predict reliably each patient's risk based on linear univariate analysis. The authors investigated a neural network to model the risk of prostate carcinoma by seven readily available clinical features.METHODSThe database for the current study comprised 3268 men recently evaluated for the early detection of prostate carcinoma. The seven clinical features evaluated included age, race, family history, International Prostate Symptom Score (IPSS), DRE, and total and complexed PSA. Three hundred forty‐eight subjects in the dataset included men with determined prostate biopsy outcomes and for whom at least 6 of 7 features were available. The dataset was divided randomly into a training set (60%) and a test set (40%), with n1/n2 cross‐validation used to evaluate model accuracy, and was modeled with linear and quadratic discriminant function analysis and a neural computational system. After a model with acceptable goodness of fit was achieved, reverse regression analysis using Wilks's generalized likelihood ratio test was performed to evaluate the statistical significance of each input variable.RESULTSThe receiving operating characteristic (ROC) area for the neural computational system in the test set was 0.825, whereas total PSA and complexed PSA alone had ROC areas of 0.678 and 0.697, respectively. The ROC area of logistic regression in the test set was 0.510, linear discriminant function analysis was 0.674, and quadratic discriminant function analysis was 0.011. All were significantly less than the ROC area of the neural computational model (all Ps < 0.002). Reverse regression based on Wilks's generalized likelihood ratio test demonstrated each input feature to be highly significant to the model (all Ps ≪ 0.000001).CONCLUSIONSThe authors modeled a combination of well described patient risk factors for prostate carcinoma using a neural computational system with acceptable goodness of fit. They demonstrated that each of the seven variates on which the model was based was critically significant to model performance. The authors presented this model for clinical use and suggested that clinicians use it in deciding to perform prostate biopsy. Cancer 2003. © 2003 American Cancer Society.
Skull base and nonskull base chordomas
Authors: Naka Takahiko , Boltze Carsten , Samii Amir , Herold Christian , Ostertag Helmut , Iwamoto Yukihide , Oda Yoshinao , Tsuneyoshi Masazumi , Kuester Doerthe , Roessner Albert 
Published: October 2003

AbstractBACKGROUNDTo the authors' knowledge, little is known regarding the relation between the proliferative ability and clinicopathologic parameters in skull base chordomas (SBCs) and nonskull base chordomas (NSBCs).METHODSThe authors investigated 122 conventional chordomas for their clinicopathologic parameters, proliferative ability (MIB‐1 labeling index [LI]) and clinical outcome.RESULTSPrimary NSBCs were found to affect more elderly patients and demonstrated a higher MIB‐1 LI compared with primary SBCs. Mitosis was more commonly noted in recurrent NSBCs compared with primary NSBCs. Apoptosis was more frequent in elderly patients than in younger patients with regard to both SBCs and NSBCs. Apoptosis also was found to be correlated with necrosis in SBCs, suggesting a common factor for the two different types of cell death. Mucoid matrix was reported to be more abundant in NSBCs than in SBCs, and appeared to occur more often in elder NSBC patients compared with younger NSBC patients. This indicates that it is produced in the later stages of tumorigenesis. In SBCs, several clinicopathologic parameters were found to be correlated with MIB‐1 LI. Among them, increased age, recurrence, and nuclear pleomorphism were the only independent factors found to indicate a higher MIB‐1 LI. No such parameters were found in NSBCs. However, in these lesions, prognosis was significantly poorer in those cases with nuclear pleomorphism compared with those without.CONCLUSIONSThe results of the current study suggest that nuclear pleomorphism is a prognostic indicator in NSBCs. The proliferative ability of SBCs appears to be closely associated with patient age, clinical status (recurrence), and nuclear pleomorphism. Cancer 2003. © 2003 American Cancer Society.
Extracellular inorganic phosphate regulates Gibbon ape leukemia virus receptor‐2/phosphate transporter mRNA expression in rat bone marrow stromal cells
Authors: Wada Keinoshin , Mizuno Morimichi , Komori Takahide , Tamura Masato 
Published: October 2003

AbstractIn mammalian cells, several observations indicate not only that phosphate transport probably regulates local inorganic phosphate (Pi) concentration, but also that Pi affects normal cellular metabolism, which in turn regulates apoptosis and the process of mineralization. To elucidate how extracellular Pi regulates cellular functions of pre‐osteoblastic cells, we investigated the expression of type III sodium (Na)‐dependent Pi transporters in rat bone marrow stromal cells and ROB‐C26 pre‐osteoblastic cells. The mRNA expression level of gibbon ape leukemia virus receptor (Glvr)‐2 was increased by the addition of Pi in rat bone marrow stromal cells, but not in ROB‐C26 or normal rat kidney (NRK) cells. In contrast, the level of Glvr‐1 mRNA was not altered by the addition of extracellular Pi in these cells. The induction of Glvr‐2 mRNA by Pi was inhibited in the presence of cycloheximide (CHX). Moreover, mitogen‐activated protein kinase (MEK) /extracellular‐signal‐regulated kinase (ERK) pathway inhibitors; U0126 (1.4‐diamino‐2, 3‐dicyano‐1, 4‐bis [2‐amino‐phenylthio] butadiene) and PD98059 (2′‐Amino‐3′‐methoxyflavone) inhibited inducible Glvr‐2 mRNA expression, but p38 MEK inhibitor SB203580 [4‐(4′‐fluorophenyl)‐2‐(4′‐methyl‐sulfinylphenyl)‐5‐(4′pyridyl) imidazole] did not inhibit the induction of Glvr‐2 mRNA expression, suggesting that extracellular Pi regulates de novo protein synthesis and MEK/ERK activity in rat bone marrow stromal cells, and through these, induction of Glvr‐2 mRNA. Although Pi also induced osteopontin mRNA expression in rat bone marrow stromal cells but not in ROB‐C26 and NRK cells, changes in cell viability with the addition of Pi were similar in both cell types. These data indicate that extracellular Pi regulates Glvr‐2 mRNA expression, provide insights into possible mechanisms whereby Pi may regulate protein phosphorylation, and suggest a potential role for the Pi transporter in rat bone marrow stromal cells. J. Cell. Physiol. 198: 40–47, 2004. © 2003 Wiley‐Liss, Inc.
Critical protein domains and amino acid residues for gating the KIR6.2 channel by intracellular ATP
Authors: Wu Jianping , Piao Hailan , Rojas Asheebo , Wang Runping , Wang Ying , Cui Ningren , Shi Yun , Chen Fuxue , Jiang Chun 
Published: October 2003

AbstractKATP channels couple intermediary metabolism to cellular excitability. Such a property relies on the inherent ATP‐sensing mechanism known to be located in the Kir6 subunit. However, the molecular basis for the ATP sensitivity remains unclear. Here we showed evidence for protein domains and amino acid residues essential for the channel gating by intracellular ATP. Chimerical channels were constructed using protein domains of Kir6.2 and Kir1.1, expressed in HEK293 cells, and studied in inside‐out patches. The N and C termini, although important, were inadequate for channel gating by intracellular ATP. Full ATP sensitivity also required M1 and M2 helices. Cytosolic portions of the M1 and M2 sequences were crucial, in which six amino acid residues were identified, i.e., Thr76, Met77, Ala161, Iso162, Leu164, and Cys166. Site‐specific mutation of any of them reduced the ATP sensitivity. Construction of these residues together with the N/C termini produced ATP sensitivity identical to the wild‐type channels. The requirement for specific membrane helices suggests that the Kir6.2 gating by ATP is not shared by even two closest relatives in the K+ channel family, although the general gating mechanisms involving membrane helices appear to be conserved in all K+ channels. J. Cell. Physiol. 198: 73–81, 2004. © 2003 Wiley‐Liss, Inc.
EGF mediates protection against Fas‐induced apoptosis by depleting and oxidizing intracellular GSH stocks
Authors: Musallam Lina , Éthier Chantal , Haddad Pierre Selim , Bilodeau Marc 
Published: October 2003

AbstractSeveral pieces of evidence have demonstrated the importance of reduction/oxidation (redox) signaling in biological processes, including sensitivity toward apoptosis. In parallel, it was recently reported that growth factors induce the generation of reactive oxygen species (ROS). Therefore, we tested the hypothesis that the anti‐apoptotic effect of epidermal growth factor (EGF) was mediated by changes in the redox state of hepatocytes through changes in GSH stocks. Isolated mouse hepatocytes were cultured and exposed to anti‐Fas stimulation in order to induce apoptosis. Cell death by apoptosis was assessed by Hoechst 33258 staining and by measuring caspase‐3 proteolysis activity. Cell treatment with EGF significantly decreased total (GSx) and reduced (GSH) glutathione levels in the presence and the absence of anti‐Fas. Furthermore, glutathione reductase activity was lower in EGF‐treated cultures (by 28%) as compared to untreated cultures which lead to a significant decline in GSH/GSx ratio. These effects were found to be EGF‐receptor tyrosine kinase activity dependent. Co‐stimulation of cells with anti‐Fas and EGF attenuated caspase‐3 activation and cell death by apoptosis by 70%. GSH monoethylester (GSHmee) significantly attenuated the effect of EGF on GSH and GSH/GSx ratio. It caused an increase in caspase‐3 activation and in the percentage of apoptotic cells in anti‐Fas + EGF‐treated cells, thus resulting in a 53% decline in the protective effect of EGF. In conclusion, EGF induces a significant and specific depletion and oxidization of intracellular GSH, paralleled by a protection against Fas‐induced apoptosis. GSH replenishment partly counteracted these effects suggesting that GSH depletion contributed to the protective effect of EGF against caspase‐3 activation and cell death by apoptosis. J. Cell. Physiol. 198: 62–72, 2004. © 2003 Wiley‐Liss, Inc.
Elevated interleukin‐9 receptor expression and response to interleukins‐9 and ‐7 in thymocytes during radiation‐induced T‐cell lymphomagenesis in B6C3F1 mice
Authors: Nishimura Mayumi , Kakinuma Shizuko , Yamamoto Daisuke , Kobayashi Yoshiro , Suzuki Gen , Sado Toshihiko , Shimada Yoshiya 
Published: October 2003

AbstractDysregulation of cytokine receptor expression and responsiveness to cytokines is hypothesized to play an important role in the development and expansion of preneoplastic cells or progression of neoplastic cells during the early and late stages of leukemogenesis. To determine the crucial changes in initiated cells that confer significant growth during the early stage of radiation‐induced lymphomagenesis, we examined both the expression of receptors for thymus‐derived cytokines and thymocyte response to cytokines before the onset of T cell lymphomas in B6C3F1 mice after split‐dose irradiation. After irradiation, thymic T cell subsets underwent delayed regeneration consisting of two phases as determined by receptor expression. The first phase occurred within 1 week post‐irradiation and was accompanied by transient expansion of T cell subsets strongly expressing receptor genes for IL‐1, IL‐2, IL‐6, IL‐7, IL‐15, and TNFα. The second phase occurred 12 weeks after irradiation and was characterized by increased expression of IL‐9Rα. Thymocytes from non‐irradiated control mice were unresponsive to IL‐9. However, IL‐9 acted synergistically with IL‐7 and PHA to stimulate the proliferation of irradiated cells during the second post‐irradiation phase. Moreover, these cells showed hyper‐responsiveness to IL‐7 or PHA alone compared to age‐matched non‐irradiated control thymocytes. These results suggest that the unusual expression of IL‐9 receptors and/or increased responsiveness of thymocytes to cytokines are key processes in the development of radiation‐induced T cell lymphomas. J. Cell. Physiol. 198: 82–90, 2004. © 2003 Wiley‐Liss, Inc.
Gonadotropin and steroid hormones stimulate proliferation of the rat ovarian surface epithelium
Authors: Stewart Sherri L. , Querec Troy D. , Gruver Briana N. , O'Hare Brendan , Babb James S. , Patriotis Christos 
Published: October 2003

AbstractThe ovarian surface epithelium (OSE) is a single layer of flattened or cuboidal cells covering the ovary. Ninety percent of all human ovarian malignancies arise from this layer of cells. Incessant ovulation, hyperovulation induced by infertility treatment, and hormone replacement therapy have been suggested as risk factors for ovarian cancer. In this study, two groups of rats, with and without surgically induced injury to the ovary, were treated with 17β‐estradiol, pregnant mare's serum gonadotropin (PMSG), human chorionic gonadotropin (hCG), or the combination PMSG/hCG, and the proliferative response of the OSE cells was measured using bromodeoxyuridne (BrdU) and 3H‐thymidine. All hormones, alone or in combination with ovarian surgery, were found to increase significantly the rate of proliferation of the rat OSE. These data demonstrate that hormones associated with infertility treatments and hormone replacement therapy, as well as injury‐ or ovulation‐induced rupture of the ovarian surface, stimulate the rat OSE, and hence could have a role in the development of ovarian cancer via proliferation‐associated mutagenesis, or alternatively, by promoting the rapid selection of OSE cells with accumulated mutations. J. Cell. Physiol. 198: 119–124, 2004. © 2003 Wiley‐Liss, Inc.
Anatomy of the crocodilian spinal vein
Authors: Zippel Kevin C. , Lillywhite Harvey B. , Mladinich Christopher R.J. 
Published: October 2003

AbstractThe crocodilian spinal vein is remarkably robust yet historically overlooked. Using corrosion casting, we describe the anatomy of this vessel and its connections with the caval and hepatic venous systems in representatives from four crocodilian genera. The spinal vein arises from an enlarged occipital sinus over the medulla and extends the entire length of the vertebral column. Unlike in squamate reptiles, the spinal vein is single (nonplexiform), voluminous, and situated dorsal to the spinal cord, and plexi lateral to the cord span between emerging intercostal veins. The connections with the other venous systems are otherwise similar to those in other tetrapods. The overall anatomy of this vessel and its abundant connections with the other venous systems indicate it likely plays a primary role in returning blood to the heart from all parts of the body. Preliminary studies of function suggest that this vessel could also play an adaptive role during basking and diving. J. Morphol. 258:327–335, 2003. © 2003 Wiley‐Liss, Inc.
Mechanisms of internalization of apoptotic and necrotic L929 cells by a macrophage cell line studied by electron microscopy
Authors: Krysko Dmitri V. , Brouckaert Greet , Kalai Michael , Vandenabeele Peter , D'Herde Katharina 
Published: October 2003

AbstractRapid and efficient phagocytic removal of dying cells is a key feature of apoptosis. In necrotic caspase‐independent modes of death, the role and extent of phagocytosis is not well documented. To address this issue, we studied at the ultrastructural level the phagocytic response to dying cells in an in vitro phagocytosis assay with a mouse macrophage cell line (Mf4/4). As target cells, murine L929sAhFas cells were induced to die by TNFR1‐mediated necrosis or by Fas‐mediated apoptosis. Apoptotic L929sAhFas cells are taken up by complete engulfment of apoptotic bodies as single entities forming a tight‐fitting phagosome, thus resembling the “zipper”‐like mechanism of internalization. In contrast, primary and secondary necrotic cells were internalized by a macropinocytotic mechanism with formation of multiple ruffles by the ingesting macrophage. Ingestion of necrotic cellular material was invariably taking place after the integrity of the cell membrane was lost and did not occur as discrete particles, in contrast to apoptotic material that is surrounded by an intact membrane. Although nuclei of necrotic cells have been observed in the vicinity of macrophages, no uptake of necrotic nuclei was observed. The present report provides a basis for future studies aimed at discovering molecular pathways that precede these diverse mechanisms of uptake. J. Morphol. 258:336–345, 2003. © 2003 Wiley‐Liss, Inc.
Conversations about the moon with prospective teachers in Japan
Authors: Suzuki Mariko 
Published: October 2003

AbstractAs an instructor in courses for prospective teachers, I am interested in my students' ideas and ways in which they reconstruct their ideas in conversations about science. In the case study presented here, I reflect upon (a) ways in which I engaged prospective teachers in thinking together about their observations of a natural phenomenon, the changing phases of the moon, and (b) the ideas that they expressed. The case study examines ways in which prospective teachers developed understandings of the sun–earth–moon system from two perspectives: as viewed from the earth and from outside the solar system. © 2003 Wiley Periodicals, Inc.Sci Ed87:892–910, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/sce.10082
From universal system of social policy to particularistic? The case of the Baltic States
Authors: Aidukaite Jolanta 
Published: October 2003

This paper compares the system of social maintenance and insurance in the Soviet Union, which was in force in the three Baltic countries before their independence, with the currently existing social security systems. The aim of the paper is to highlight the forces that have influenced social policy transformation from its former highly universal, however authoritarian form, to the less universal, social insurance-based systems of present day Lithuania, Latvia and Estonia.
It will be demonstrated that the welfare–economy nexus is not the only important factor in the development of social programs. Rather, social policy should be studied as if embedded in the political, historical and cultural aspects of a given society. The people’s attitude towards distributive justice will be highlighted as being one of the most important factors for either social policy shortcomings or expansion.
This paper takes steps to combine quantitative and qualitative data.
Credit card rates and consumer search
Authors: Berlin Mitchell , Mester Loretta J. 
Published: October 2003

AbstractCredit card rates have tended to be higher and stickier than other loan rates but have fallen over the past decade. Some argue this decline is due to a reduction in consumer search costs. Our evidence suggests search costs are not the best explanation for the decline. We test whether consumer search models explained credit card pricing in the 1980s when search costs were thought to be significant. We find that the distributions of rates were inconsistent with those derived from many models of search. Proposals for stricter disclosure requirements may have less effect on equilibrium credit card rates than intended.