bluuebunny/crossref_metadata_2025_split huggingface dataset:
A systematic numerical method to analyze hybrid networks composed of linear/nonlinear lumped elements and transmission lines with distributed sources
Authors: Ichikawa Satoshi , Tanaka Ryuichirou 
Published: March 2004

AbstractThis paper describes a systematic numerical analysis method for hybrid networks consisting of lumped and distributed elements. The lumped element circuit portion consists of linear and nonlinear elements while the distributed circuit portion consists of transmission lines with loss terms that have frequency dependence. The shape of the transmission line is not only uniform but also may be nonuniform due to limitations in implementation. The power supply is not only the independent source but may also be a distributed source induced by an external incident electromagnetic field. The transmission line section is formulated in the complex frequency domain (s domain) by means of the Laplace transform. If the lumped element circuit section consists only of linear time‐invariant elements, then the formulation is by the state equation derived from the telegrapher's equation with the voltage and current vectors on the transmission line as the variables. For the analysis of the entire circuit, the numerical inverse Laplace transform is applied to the results obtained in the s domain. If the lumped element circuit section contains nonlinear elements, then the transmission line section is formulated by transforming the results based on the scattering matrix with the incident voltage and reflected voltage vectors at both ends of the transmission line in the s domain into the time domain. The analysis of the entire circuit is carried out in the time domain by discretization. © 2004 Wiley Periodicals, Inc. Electron Comm Jpn Pt 3, 87(7): 1–14, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjc.10160
Interphase fluorescence in situ hybridization for detection of 8q24/MYC breakpoints on routine histologic sections: Validation in Burkitt lymphomas from three geographic regions
Authors: Haralambieva Eugenia , Schuuring Ed , Rosati Stefano , van Noesel Carel , Jansen Patty , Appel Inge , Guikema Jeroen , Wabinga Henry , Fernando Bleggi‐Torres Luiz , Lam King , van den Berg Eva , Mellink Clemens , van Zelderen‐Bhola Shama , Kluin Philip 
Published: March 2004

AbstractA chromosomal translocation involving the MYC gene is characteristic of Burkitt lymphoma (BL) and represents a molecular disease marker with diagnostic and clinical implications. The detection of MYC breakpoints is hampered by technical problems, including the distribution of the breakpoints over a very large genomic region of approximately 1,000 kb. In this article, we report on the testing and validation of a segregation fluorescence in situ hybridization (FISH) assay for MYC breakpoints on a large series of BLs. A contig of overlapping genomic clones was generated, and two probe sets flanking the MYC gene were selected. Both probe sets were tested in an interphase FISH segregation assay on 8 B‐cell lymphoma cell lines and 32 lymphoma samples with proved 8q24/MYC abnormalities and validated in 47 BLs from The Netherlands, Brazil, and Uganda. MYC translocation breakpoints were identified in 98% of the tumors of the test series and in 89% of the cases of the validation series. In 89% of all positive samples, the breakpoints were located between 190 kb 5′ and 50 kb 3′ of MYC. Nine cases had more distant breakpoints, and in one patient an insertion of MYC into the IGH region was detected. In two of the three BLs lacking CD10 expression, no breakpoint could be detected, suggesting that CD10 is a discriminative marker of BL. We did not find consistent differences between BL and atypical BL in incidence of an MYC breakpoint. © 2004 Wiley‐Liss, Inc.
Identification of preleukemic precursors of hyperdiploid acute lymphoblastic leukemia in cord blood
Authors: Maia Ana Teresa , Tussiwand Roxane , Cazzaniga Giovanni , Rebulla Paolo , Colman Susan , Biondi Andrea , Greaves Mel 
Published: March 2004

AbstractPrevious studies involving identical twins with concordant leukemia and retrospective scrutiny of archived neonatal blood spots have shown that common chromosome translocations of pediatric leukemia frequently arise before birth. The IGH/TCR clonotypic sequences used as surrogate molecular markers suggest this is also likely to be true for hyperdiploid acute lymphoblastic leukemia (ALL). Yet evidence that hyperdiploidy itself is an early or initiating event occurring prenatally has been limited. Now, however, we can provide direct evidence of this from our identification of CD34+/CD19+ B‐lineage progenitor cells with triploid chromosomes in the stored cord blood of an individual who subsequently developed hyperdiploid ALL. © 2004 Wiley‐Liss, Inc.
ASK1 (MAP3K5) as a potential therapeutic target in malignant fibrous histiocytomas with 12q14–q15 and 6q23 amplifications
Authors: Chibon Frédéric , Mariani Odette , Derré Josette , Mairal Aline , Coindre Jean‐Michel , Guillou Louis , Sastre Xavier , Pédeutour Florence , Aurias Alain 
Published: March 2004

AbstractMalignant fibrous histiocytomas (MFHs) are aggressive tumors without any definable line of differentiation. We recently demonstrated that about 20% of them are characterized by high‐level amplifications of the 12q14–q15 chromosome region, associated with either 1p32 or 6q23 band amplification. This genetic finding, very similar to that in well‐differentiated liposarcomas, strongly suggests that these tumors actually correspond to undifferentiated liposarcomas. It also suggests that the lack of differentiation could be the consequence of amplification of target genes localized in the 1p32 or 6q23 bands. We report here the characterization by array CGH of the 6q23 minimal region of amplification. Our findings demonstrate that amplification and overexpression of ASK1 (MAP3K5), a gene localized in the 6q23 band and encoding a mitogen‐activated protein kinase kinase kinase of the JNK‐MAPK signaling pathway, could inhibit the adipocytic differentiation process of the tumor cells. Treatment of a cell line with specific inhibitors of ASK1 protein resulted in the bypass of the differentiation block and induction of a strong adipocytic differentiation. These observations indicate that ASK1 is a target for new therapeutic management of these aggressive tumors. © 2004 Wiley‐Liss, Inc.
Delineation of a minimal region of deletion at 6q16.3 in follicular lymphoma and construction of a bacterial artificial chromosome contig spanning a 6‐megabase region of 6q16–q21
Authors: Henderson Laura‐Jane , Okamoto Ichiro , Lestou Valia S. , Ludkovski Olga , Robichaud Marc , Chhanabhai Mukesh , Gascoyne Randy D. , Klasa Richard J. , Connors Joseph M. , Marra Marco A. , Horsman Douglas E. , Lam Wan L. 
Published: March 2004

AbstractRegional deletions of 6q are frequent karyotypic alterations in malignant lymphoma and are associated with an adverse clinical outcome. One such region of recurrent deletion is 6q16−q21; however, the specific genes affected have not been identified. Our objective in this study was to identify cases with deletion of 6q16−q21 in follicular lymphoma and to define a minimal region of deletion. A physical map of 6q16.2−q21 was constructed using map information from both sequence‐based and bacterial artificial chromosome (BAC) fingerprint–based maps. Forty‐three BAC clones spanning a 6‐Mb region of 6q16.2–q21 were identified and obtained from the RP‐11 library. Selected BACs were fluorescence‐labeled and hybridized to a series of 34 follicular lymphomas with a regional 6q deletion detected by G banding. Twenty‐four cases with deletion of the 6q16.3 region were detected. A minimal deletion of 2.3 Mb was defined. Our study has identified a limited region of deletion of 6q16.3 that may implicate four known genes in follicular lymphoma and possibly in other cancers. A BAC contig spanning a 6‐Mb region has been anchored to the 6q16.2–q21 region. This map represents a useful resource for gene identification in this region, not only in lymphoma but also in other neoplasms with 6q alterations. © 2004 Wiley‐Liss, Inc.
Molecular and cytogenetic characterization of a novel translocation t(4;22) involving the breakpoint cluster region and platelet‐derived growth factor receptor–alpha genes in a patient with atypical chronic myeloid leukemia
Authors: Safley Anne Michele , Sebastian Siby , Collins Timothy S. , Tirado Carlos A. , Stenzel Timothy T. , Gong Jerald Z. , Goodman Barbara K. 
Published: March 2004

AbstractWe report a case of BCR‐ABL‐negative atypical chronic myeloid leukemia (CML) with translocation t(4;22) (q12;q11.2) juxtaposing the breakpoint cluster region (BCR) and platelet‐derived growth factor receptor–alpha (PDGFRA) genes. The patient was a 57‐year‐old man with a history of stage IV diffuse large B‐cell lymphoma, status post–6 cycles of combination chemotherapy in 1999, who presented in August 2002 with enlarged lymph nodes, anemia, and marked leukocytosis (50 × 109 g/dL) consistent with a myeloproliferative disorder (MPD). A bone marrow biopsy showed granulocytic hyperplasia, neutrophilia, and mild eosinophilia. Initial cytogenetic evaluation by interphase FISH for BCR‐ABL, to rule out a translocation 9;22, showed a variant signal pattern consistent with rearrangement of BCR at 22q11.2, but not ABL at 9q34. Analysis of the patient's cDNA by polymerase chain reaction (PCR) for BCR‐ABL was negative. Cytogenetic analysis showed an abnormal karyotype with rearrangement of chromosomes 4 and 22. PCR amplification and subsequent sequence analysis demonstrated an in‐frame 5′‐BCR/3′‐PDGFRA fusion in the patient's cDNA. PDGFRA encodes a receptor tyrosine kinase and shares structural and organizational homology with the KIT and CSf1R receptor genes. However, although the incidence of MPD involving translocations of PDGFRB has been well established, to our knowledge there are only two previous reports describing a BCR‐PDGFRA fusion gene, in 3 patients diagnosed with atypical CML. Here, we report the molecular and cytogenetic characterization of a patient with BCR‐PDGFRA‐positive MPD who had a complete hematologic response after treatment with imatinib mesylate. © 2004 Wiley‐Liss, Inc.
Estrogen receptor α (ESR1) mutant A908G is not a common feature in benign and malignant proliferations of the breast
Authors: Tebbit Christopher L. , Bentley Rex C. , Olson John A. , Marks Jeffrey R. 
Published: March 2004

AbstractAlterations in estrogen responsive pathways are thought to contribute to benign and malignant breast disease. It has been reported previously that more than a third of typical epithelial hyperplasia lesions harbor the missense mutation A908G in the estrogen receptor α (ESR1) gene. This substitution of an arginine for a lysine at codon 303 was reported to confer mitogenic hypersensitivity to estrogen. To explore this finding further, we analyzed ESR1 for this mutation in a series of breast tissues ranging from typical hyperplasia to invasive cancer. In contrast to previous studies, no evidence for this mutation was found in 36 invasive cancers, 11 in situ carcinomas, 14 epithelial hyperplasias with atypia, 11 epithelial hyperplasias without atypia, and 11 breast cancer cell lines. These results indicate that ESR1 mutant A908G does not occur with significant frequency in either benign or malignant proliferations of breast epithelia. © 2004 Wiley‐Liss, Inc.
Gene amplification of atypical PKC‐binding PARD3 in radiation‐transformed neoplastic retinal pigment epithelial cell lines
Authors: Zitzelsberger Horst , Hieber Ludwig , Richter Hedwig , Unger Kristian , Briscoe Cecilia V. , Peddie Clare , Riches Andrew 
Published: March 2004

AbstractNeoplastic transformation induced by ionizing radiation was studied using a human retinal pigment epithelial cell line immortalized by telomerase. Radiation‐transformed cell clones were tumorigenic in athymic mice and were analyzed by G‐banding and comparative genomic hybridization (CGH). Radiation‐transformed cloned cell lines and cell lines derived from tumors produced in athymic nude mice following transplantation exhibited a recurrent karyotype:45,XX,der(10),‐13. CGH showed an amplification of 10p11.2 and a deletion of the remaining 10p. Positional cloning of the amplified region by FISH analysis and subsequent sequence analysis of BAC clones showing amplified FISH signals identified the candidate gene PARD3. This gene also was found to be transcriptionally expressed at an increased level. The findings indicate that PARD3 may play an important role in radiation‐induced carcinogenesis of RPE cells. This is the first evidence for PARD3 amplification in human cancer cells. © 2004 Wiley‐Liss, Inc.
Atomic structure of a CK2α human kinase by microfocus diffraction of extra‐small microcrystals grown with nanobiofilm template
Authors: Pechkova Eugenia , Nicolini Claudio 
Published: March 2004

AbstractExtra‐small microcrystals of a human kinase CK2α were obtained for the first time by the optimization of a recent protein crystallization method based on highly packed protein nanofilm template. Protein crystal induction and growth appear indeed optimal at high surface pressure of the film template yielding high protein orientation and packing. The resulting extra‐small CK2α microcrystals (of about 20 μm in diameter) was subsequently used for synchrotron radiation diffraction data collection, which proves possible by means of the Microfocus Beamline at the ESRF Synchrotron in Grenoble. The quality of the resulting crystal diffraction patterns and of its resulting atomic structure at 2.4 Å resolution proves the unique validity of the above two combined frontier technologies in defining a new approach to structural proteomics capable to solve the atomic structure of proteins so far never been crystallized and of pharmaceutical relevance. Physical explanation in terms of template dipole moments and possibility of generalization of this method to the wide class of proteins not yet crystallized are finally discussed. The structure of our CK2α mutant is in the Protein Data Bank (PDB ID Code 1NA7, deposited on 27 November 2002). © 2004 Wiley‐Liss, Inc.
Inhibition of AP‐1 transcription activator induces myc‐dependent apoptosis in HL60 cells
Authors: Park Seyeon , Hahm Eun‐Ryeong , Lee Dug‐Keun , Yang Chul‐Hak 
Published: March 2004

AbstractTranscriptional activation of AP‐1 is intricately involved in cell proliferation and transformation. The natural product, nordihydroguaiaretic acid (NDGA) shows an inhibitory effect on the binding of jun/AP‐1 protein to the AP‐1 site in 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA)‐stimulated HL60 cells. The NDGA inhibits the auto‐regulated de novo synthesis of c‐jun mRNA in TPA‐stimulated HL60 cells. Our data also determine that this compound induces proliferation inhibition and apoptosis in human leukemia HL60 cells. To obtain information on the functional role of the AP‐1 inhibition by NDGA in apoptosis signaling, the effects of pharmacological inhibition of AP‐1 binding on c‐myc, p53, and bax protein level were determined. Our results indicate that treatment of cells with NDGA enhances c‐myc, p53, and bax protein levels. To rule out the possibility that NDGA will induce apoptosis because of the effects on proteins other than AP‐1, we investigated the effect of another AP‐1 inhibitor, SP600125, which is specific to Jun‐N‐terminal kinase. SP600125 decreased not only the phosphorylation level of jun protein but also AP‐1/DNA binding activity. Also, apoptosis was observed to be induced by SP600125, concomitant with the increase in c‐myc, p53, and bax protein level. In addition, apoptosis induced by both AP‐1 inhibitors was accompanied by the activation of a downstream apoptotic cascade such as caspase 9, caspase 3, and poly[ADP‐ribose]polymerase (PARP). When the cells were treated with NDGA or SP600125 in the presence of antisense c‐myc oligonucleotides, apoptosis was not observed and an increase of c‐myc, p53, and bax proteins was not manifested. All these results show that the inhibition of the transcription factor AP‐1 action is related with either the drug‐induced apoptosis or the drug toxicity of the HL60 cells. The apoptosis induced by AP‐1 inhibition may be dependent on c‐myc protein levels suggesting that the c‐myc protein induces apoptosis at a low level of AP‐1 binding activity. Altogether, our findings suggest that the presence of the AP‐1 signal acts as a survival factor that determines the outcome of myc‐induced proliferation or apoptosis. © 2004 Wiley‐Liss, Inc.
Functional idiotypic mimicry of an adhesion‐ and differentiation‐promoting site on acetylcholinesterase
Authors: Johnson Glynis , Moore Samuel W. 
Published: March 2004

AbstractAcetylcholinesterase mediates cell adhesion and neurite outgrowth through a site associated with the peripheral anionic site (PAS). Monoclonal antibodies raised to this site block cell adhesion. We have raised anti‐idiotypic antibodies to one of these antibodies. The anti‐idiotypic antibodies recognized the immunogenic antibody and non‐specific mouse IgG, but not acetylcholinesterase. Five antibodies (out of 143 clones, an incidence of 3.5%) were able to promote neurite outgrowth in human neuroblastoma cells in vitro in a similar manner to acetylcholinesterase itself, suggesting that these antibodies carry an internal image of the neuritogenic site. Two of the antibodies were significantly more effective (P < 0.01) than acetylcholinesterase in this regard. The antibodies also bound specifically to mouse laminin‐1 and human collagen IV, as does acetylcholinesterase. This binding was displaced by unlabelled antibody, as well as by acetylcholinesterase itself, indicating competition with acetylcholinesterase. We have also investigated the development of anti‐anti‐idiotypic antibodies in mice in vivo, and have observed that four of these (out of 318 clones, an incidence of 1.26%) mimic the idiotypic antibody and abrogate adhesion in neuroblastoma cells. We have thus demonstrated functional mimicry of the neuritogenic site on acetylcholinesterase in anti‐idiotypic antibodies, enhancement of this activity in one antibody, and mimicry of the idiotypic antibody site in anti‐anti‐idiotypic antibodies. Implications of these findings for differentiation‐promoting cancer therapy are discussed. © 2004 Wiley‐Liss, Inc.
Signaling pathway of magnolol‐stimulated lipolysis in sterol ester‐loaded 3T3‐L1 preadipocyes
Authors: Huang Shih‐Horng , Shen Wung‐Jing , Yeo Hui‐Lin , Wang Seu‐Mei 
Published: March 2004

AbstractThe aims of the present study were to examine the effect of magnolol on lipolysis in sterol ester (SE)‐loaded 3T3‐L1 preadipocytes and to determine the signaling mechanism involved. We demonstrate that magnolol treatment resulted in a decreased number and surface area of lipid droplets, accompanied by release of glycerol. The lipolytic effect of magnolol was not mediated by PKA based on the facts that magnolol did not induce an elevation of intracellular cAMP levels, and protein kinase A (PKA) inhibitor KT5720 did not block magnolol‐induced lipolysis. Calcium/calmodulin‐dependent protein kinase (CaMK) was involved in this signaling pathway, since magnolol‐induced a transient rise of intracellular [Ca2+] and Ca2+ influx across the plasma membrane, and CaMK inhibitor significantly abolished magnolol‐induced lipolysis. Moreover, magnolol increased the relative levels of phosphorylated extracellular signal‐related kinases (ERK1 and ERK2). In support of the involvement ERK, we demonstrated that magnolol‐induced lipolysis was inhibited by PD98059, an inhibitor of mitogen‐activated protein kinase kinase (MEK), and PD98059 reversed magnolol‐induced ERK phosphorylation. Further, the relationship between CaMK and ERK was connected by the finding that CaMK inhibitor also blocked magnolol‐induced ERK phosphorylation. Taken together, these findings suggest that magnolol‐induced lipolysis is both CaMK‐ and ERK‐dependent, and this lipolysis signaling pathway is distinct from the traditional PKA pathway. ERK phosphorylation is reported to enhance lipolysis by direct activation of hormone sensitive lipase (HSL), thus magnolol may likely activate HSL through ERK and increase lipolysis of adipocytes. © 2004 Wiley‐Liss, Inc.
Interleukin (IL)‐17 enhances tumor necrosis factor‐α‐stimulated IL‐6 synthesis via p38 mitogen‐activated protein kinase in osteoblasts
Authors: Tokuda Haruhiko , Kanno Yosuke , Ishisaki Akira , Takenaka Motoki , Harada Atsushi , Kozawa Osamu 
Published: March 2004

AbstractInflammatory cytokines are well known to play crucial roles in the pathogenesis of rheumatoid arthritis. Among them, interleukin (IL)‐17 is a cytokine that is mainly synthesized by activated T cells and its receptors are present in osteoblasts. The synthesis of IL‐6, known to stimulate osteoclastic bone resorption, is reportedly responded to bone resorptive agents such as tumor necrosis factor‐α (TNF‐α) in osteoblasts. It has been reported that IL‐17 enhances TNF‐α‐stimulated IL‐6 synthesis in osteoblast‐like MC3T3‐E1 cells. We previously showed that sphingosine 1‐phosphate (S1‐P) mediates TNF‐α‐stimulated IL‐6 synthesis in these cells. In the present study, we investigated the mechanism of IL‐17 underlying enhancement of IL‐6 synthesis in MC3T3‐E1 cells. IL‐17 induced phosphorylation of p38 mitogen‐activated protein (MAP) kinase. SB203580 and PD169316, specific inhibitors of p38 MAP kinase, significantly reduced the enhancement by IL‐17 of TNF‐α‐stimulated IL‐6 synthesis. IL‐17 also amplified S1‐P‐stimulated IL‐6 synthesis, and the amplification by IL‐17 was suppressed by SB203580. Anisomycin, an activator of p38 MAP kinase, which alone had no effect on IL‐6 level, enhanced the IL‐6 synthesis stimulated by TNF‐α. SB203580 and PD169316 inhibited the amplification by anisomycin of the TNF‐α‐induced IL‐6 synthesis. Taken together, our results strongly suggest that IL‐17 enhances TNF‐α‐stimulated IL‐6 synthesis via p38 MAP kinase activation in osteoblasts. © 2004 Wiley‐Liss, Inc.
Low doses and high doses of heparin have different effects on osteoblast‐like Saos‐2 cells in vitro
Authors: Hausser Heinz‐Juergen , Brenner Rolf E. 
Published: March 2004

AbstractLong‐term treatment with heparin has been associated with an increased risk of osteoporosis. Given the importance of heparan sulfate proteoglycans for bone metabolism, it can be anticipated that heparin due to its structural similarity with heparan sulfate chains somehow interferes with the biological activities of these cell surface‐ and extracellular matrix‐associated molecules. Initially in order to study the effect(s) of heparin on osteoblasts that possibly contribute to the development of heparin‐induced osteoporosis, we treated osteoblast‐like Saos‐2 cells in monolayer culture for different periods of time with different concentrations of heparin. None of the heparin concentrations tested led to an inhibition of osteoblast proliferation during the early proliferative phase. After longer incubation times, however, cultures treated with higher concentrations of heparin (≥5 μg/ml) exhibited a reduction in cell number as well as an inhibition of matrix deposition and mineralization. These effects could not be observed with lower heparin concentrations. On the contrary, low concentrations of heparin (5–500 ng/ml) even promoted matrix deposition and its subsequent mineralization. Apparently, heparin has a biphasic effect on osteoblast‐like Saos‐2 cells, being inhibitory at high concentrations but stimulatory at low concentrations. These results imply that heparin at concentrations well below those used for antithrombotic therapy might eventually turn out to be beneficial for bone formation. © 2004 Wiley‐Liss, Inc.