bluuebunny/crossref_metadata_2025 huggingface dataset:
Diesel particulate matter and NOx removals using a pulsed corona surface discharge
Authors: Yao S. , Okumoto M. , Yashima T. , Shimogami J. , Madokoro K. , Suzuki E.
Published: March 2004

A pulsed corona surface discharge (PCSD) system was established for particulate matter (PM) and NOx removals from a diesel engine. The PCSD was carried out with a dielectric barrier discharge (DBD) reactor and a pulse power supply at atmospheric pressure and room temperature. The DBD reactor consisted mainly of an alumina (Al2O3) tube and a stainless steel rod (cathode) inserted in the alumina tube, and an aluminum coil (anode) wound on the outside surface of the Al2O3 tube. Pulse voltage was applied to the outside Al coil and stainless steel rod. PM was removed at a rate of 89% at maximum with 40% NOx removal. Relations of pulse voltage and frequency to PM and NOx removals were investigated. PM was oxidized by NO2 and other kinds of active oxygen species, such as O and O3 from plasma discharges. A surface adsorption/desorption and PM oxidation model of PM removal was established. The kinetic equations and their constants were given. © 2004 American Institute of Chemical Engineers AIChE J, 50:715–721, 2004
Social behavior profile in young males with fragile X syndrome: Characteristics and specificity
Authors: Kau Alice S.M. , Tierney Elaine , Bukelis Irena , Stump Mariah H. , Kates Wendy R. , Trescher William H. , Kaufmann Walter E.
Published: March 2004

The present study characterizes distinctive and specific features of social behavior impairment, termed social behavior profile (SBP), in young males with fragile X syndrome (FraX). Fourteen males with FraX and autism (FraX+Aut), ages 3–8 years, were compared with either 41 FraX boys without autism (Aut), 7 age‐matched males with developmental language delay and autism (DLD+Aut), or with 11 boys with non‐selected (for language delay) idiopathic autism (IA), on several standardized instruments assessing social behavior and autistic features (i.e., autism diagnostic interview‐revised, ADI‐R). We found that FraX+Aut subjects displayed more impairment in overall cognition, problem/aberrant behavior, and adaptive behavior than the rest of the FraX cohort, even when individuals with pervasive developmental disorder (PDD) were included in the latter. Compared to both DLD+Aut and IA, FraX+Aut males were less impaired in ADI‐R reciprocal social interaction (RECS) domain. However, boys with FraX+Aut were in general comparable to DLD+Aut subjects in problem/aberrant and adaptive behaviors. Based on the contrast between FraX+Aut and non‐autistic FraX and DLD+Aut, we were able to identify measures (e.g., child behavior checklist (CBCL) withdrawn subscale) that better define social interaction impairment in FraX. Comparisons with DLD+Aut and IA led to the conclusion that communication impairment (COMM) and stereotypic behavior contribute relatively more to the diagnosis of autism in FraX+Aut. In agreement with recent studies, our data suggest that FraX+Aut, and more generally SBP, is a distinctive subphenotype among boys with FraX, which may share some pathophysiological mechanisms with IA. © 2004 Wiley‐Liss, Inc.
Growth of heterokaryotic monozygotic twins discordant for Ullrich–Turner syndrome during the first years of life
Authors: Rohrer T.R. , Gassmann K.F. , Rauch A. , Pfeiffer R.A. , Doerr H.G.
Published: March 2004

The rare observation of different karyotypes in monozygotic (MZ) twins, i.e., heterokaryotic monozygosity, occurs due to chromosomal aberration in one of the twins after separation of the embryos. We report on the differences of heterokaryotic MZ Turkish twins who are discordant for Ullrich–Turner syndrome. Chromosomal analyses from peripheral lymphocytes revealed a 45,X/46,XX mosaicism in both twins. FISH analyses of buccal smears showed 99% of nuclei 45,X in twin A and 98% of nuclei 46,XX in twin B. These results are consistent with a non‐mosaic 45,X and 46,XX karyotype, respectively. The girls showed a different growth pattern in the first years. As their genotype should be identical except for the number of X chromosomes, the difference in phenotype may be a pure result of loss of one X chromosome in the affected girl. Special interest is set on the spontaneous and growth hormone induced growth of the twins. © 2004 Wiley‐Liss, Inc.
A study of reciprocal translocations and inversions detected by light microscopy with special reference to origin, segregation, and recurrent abnormalities
Authors: Youings Sheila , Ellis Katrina , Ennis Sarah , Barber John , Jacobs Patricia
Published: March 2004

We analyzed 448 independently ascertained reciprocal translocations and 220 inversions referred to our diagnostic laboratory. Twenty‐eight percent of the translocations and 8.5% of the inversions arose de novo, the proportion being influenced by the method of ascertainment. It was highest, 47%, among translocations ascertained through an abnormal phenotype. With the exception of the 3:1 unbalanced segregants, the remainders were equally likely to have been paternally or maternally inherited. The segregation from balanced translocation and inversion carriers showed an equal number of offspring with a normal chromosome constitution and with a balanced rearrangement. The number of unbalanced segregants among the translocations was 2.7% where the proband was balanced, and 19.2% where the proband was unbalanced. There was only a single unbalanced inversion. A search for recurring translocations showed only the well documented t(11;22) to occur with unusual frequency in our series and those of others, and we concluded that the few other translocations that were seen on more than one occasion were likely to be identical by descent (IBD). Similarly the majority of the recurring inversions, with the exception of “common variants,” seemed likely to be IBD. However, eight inversions recurred in our data and in most other series and may well be genuine independent rearrangements. A search of the known olfactory receptor (OR) loci and duplicons suggested that such sequences did not form an important contribution to the breakpoints of recurring rearrangements detected by light microscopy. © 2003 Wiley‐Liss, Inc.
XX‐agonadism in a fetus with multiple congenital anomalies
Authors: Woo Hennie H.N. , Lo Ivan F.M. , Tse H.Y. , Lam Stephen T.S. , Tang C.H.
Published: March 2004

We report on an 18‐week gestation fetus with 46,XX karyotype, gonadal agenesis, meningo‐encephalocele, spina bifida, omphalocele, webbing of right upper limb, deformed right clavicle and right sided ribs, absent interventricular septum, hypoplastic aorta, hypoplastic spleen, and single umbilical artery. This case is similar to the one previously described by Kennerknecht et al. in 1997 and may represent a unique syndrome. © 2003 Wiley‐Liss, Inc.
Psychosocial impact of predictive testing for myotonic dystrophy type 1
Authors: Prévost Claude , Veillette Suzanne , Perron Michel , Laberge Claude , Tremblay Carmen , Auclair Julie , Villeneuve Josée , Tremblay Marc , Mathieu Jean
Published: March 2004

In the Saguenay‐Lac‐Saint‐Jean region (Quebec, Canada), a predictive DNA‐testing program for myotonic dystrophy type 1 (DM1) has been available as a clinical service since 1988. From 1 to 12 years (median, 5 years) after receiving predictive testing, a total of 308 participants (44 carriers and 264 non‐carriers) answered a questionnaire to determine the psychosocial impact of this genetic testing. The main reasons for wanting to be tested were to learn if children are at risk for DM1 or for reproductive decision making (75%) and to relieve the uncertainty for themselves (17%). The majority of participants (96.1%) remembered correctly their test result. At the time of the survey, the perception of the general well‐being, the psychological distress (Psychiatric Symptom Index), and the self‐esteem (Rosenberg Self‐Esteem Scale) were similar in carriers, in non‐carriers, and in the reference (Quebec) population. When participants indicated a change in different aspects of their lives following predictive testing, it was perceived as a change for the better by non‐carriers and as a change for the worse by carriers. Nevertheless, for a majority of carriers and of non‐carriers, the test result did not bring changes in their lives. All respondents believed that predictive testing should be available for the at‐risk population and the vast majority of carrier and of non‐carriers would recommend the use of predictive testing to their family members. Predictive testing for individuals at‐risk of DM1 can be offered safely within a well‐organized clinical and genetic counseling program that includes careful pre‐test counseling, pre‐test clinical assessment, post‐test psychological support, and follow‐up for those identified as carriers. © 2003 Wiley‐Liss, Inc.
Five haplotypes account for fifty‐five percent of ATM mutations in Brazilian patients with ataxia telangiectasia: Seven new mutations
Authors: Coutinho Gabriela , Mitui Midori , Campbell Catarina , Costa Carvalho Beatriz T. , Nahas Shareef , Sun Xia , Huo Yong , Lai Chih‐hung , Thorstenson Yvonne , Tanouye Robert , Raskin Salmo , Kim Chong A. , Llerena Juan , Gatti Richard A.
Published: March 2004

We have studied the molecular genetics of 27 Brazilian families with ataxia telangiectasia (AT). Five founder effect haplotypes accounted for 55.5% of the families. AT is an autosomal recessive disorder of childhood onset characterized by progressive cerebellar ataxia, ocular apraxia, telangiectasia, immunodeficiency, radiation sensitivity, chromosomal instability, and predisposition to cancer. The ATM gene spans more than 150 kb on chromosome region 11q23.1 and encodes a product of 3,056 amino acids. The ATM protein is a member of the phosphatidylinositol 3‐kinase (PI‐3K) family of proteins and is involved in cell cycle control and DNA repair pathways. DNA was isolated from lymphoblastoid cell lines and haplotyped using four STR markers (D11S1818, NS22, D11S2179, D11S1819) within and flanking the ATM gene; all allele sizes were standardized in advance. In addition to the STR haplotypes, SNP haplotypes were determined using 10 critical polymorphisms. The entire gene was screened sequentially by protein truncation testing (PTT), single strand conformation polymorphism (SSCP), and then denaturing high performance liquid chromatography (dHPLC) to identify the disease‐causing mutations. Of the expected 54 mutations, 50 were identified. All mutations but one, led to a truncated or null form of the ATM protein (nonsense, splice site, or frameshift). Five families (18.5%) carried a deletion of 3450nt (from IVS28 to Ex31), making this one of the two most common Brazilian mutations. Mutations were located throughout the entire gene, with no clustering or hotspots. Standardized STR haplotype analysis greatly enhanced the efficiency of mutation screening. © 2003 Wiley‐Liss, Inc.
Absolute configuration of chiral terpenes in marking pheromones of bumblebees and cuckoo bumblebees
Authors: Luxová Anna , Urbanová Klára , Valterová Irena , Terzo Michael , Borg‐Karlson Anna‐Karin
Published: March 2004

The absolute configurations of citronellol, 2,3‐dihydrofarnesol, and 2,3‐dihydrofarnesal in male marking pheromones of seven species of bumblebees and cuckoo bumblebees were determined by enantioselective gas chromatography on a capillary column coated with 60% heptakis(2,3‐di‐O‐acetyl‐6‐O‐TBDMS)‐β‐cyclodextrin in polysiloxane PS 268. Pure (−)‐S‐enantiomers of all three terpenes were found in the labial glands of all investigated specimens of the following species: Bombus (Bombus) terrestris, B. (Bombus) lucorum, B. (Pyrobombus) pratorum, B. (Pyrobombus) pyrenaeus, B. (Pyrobombus) jonellus, B. (Pyrobombus) impatiens, and the cuckoo bumblebee B. (Ashtonipsithyrus) bohemicus. Within species, specimens were collected at different localities and in different years. Except for 2,3‐dihydrofarnesol in B. terrestris, this is the first report on the absolute configuration of terpenes in marking pheromones of bumblebees. Chirality 16:228–233, 2004. © 2004 Wiley‐Liss, Inc.
Circular dichroism of 1,3‐dioxane‐type (2′‐naphthyl)methylene acetals of glycosides
Authors: Kurtán Tibor , Borbás Anikó , Szabó Zoltán B. , Lipták András , Bényei Attila , Antus Sándor
Published: March 2004

The CD spectra are reported for a series of 1,3‐dioxane‐type 4,6‐O‐(2′‐naphthyl)methylene acetals of carbohydrates with and without interacting aromatic protective groups on the C‐1, C‐2, and C‐3 hydroxy groups. In the absence of interacting chromophores, the signs of the 1B transitions are not sensitive to the configuration of C‐4, while the signs of the weak 1La bands are opposite in the galacto and gluco derivatives. The equatorial parallel conformation is found to be the preferred conformation of the 2‐naphthyl group in the solid state by X‐ray diffraction. The intense 1Ba and 1Bb transitions of the naphthalene chromophore allowed a safe configurational assignment by exciton coupled interaction with the aromatic protective groups in para‐methoxyphenyl‐β‐D‐glycosides. The origin of the observed CEs were deduced and the additivity of the interactions was studied. The direction of the hydrogenolytic cleavage of 4,6‐O‐(2′‐naphthyl)methylene acetal of carbohydrates could also be detected by the 1Bb transition of the 2‐naphthyl chromophore. Chirality 16:244–250, 2004. © 2004 Wiley‐Liss, Inc.
Chiral recognition ability of curdlan triacetate: solvent and temperature effects
Authors: Toga Yuzo , Ichida Akito , Shibata Tohru , Tachibana Kozo , Namikoshi Hajime
Published: March 2004

The chiral recognition ability of the chiral stationary phase (CSP) consisting of curdlan (β‐1,3‐glucan) triacetate coated on silica gel was clearly changed by the contacting solvents and heat treatment. The chiral recognition ability significantly decreased, particularly at temperatures above 45°C, depending on the racemates. The molecular weight of the curdlan triacetate slightly influenced its ability. The recognition abilities of curdlan tricetate that was lost by heat treatment were partially recovered by contact with methanol. However, when it was contacted with ethanol a different selectivity was observed. The labile chiral recognition ability of curdlan triacetate is in striking contrast to the very stable chiral recognition of cellulose (β‐1,4‐glucan) triacetate (Chiralcel OA). This difference may be ascribed to the conformational stability of the acetates consisting of curdlan (β‐1,3‐glucan) and cellulose (β‐1,4‐glucan) with different sugar linkages. Chirality 16:272–276, 2004. © 2004 Wiley‐Liss, Inc.
Placement algorithm for rectilinear core cells by multilayered parametric BSG
Authors: Sakanushi Keishi , Nakatake Shigetoshi , Kajitani Yoji
Published: March 2004

Although the bounded sliceline grid (BSG) is an effective data structure for treating rectangular placement, it needs to deal with more complicated rectilinear figures such as L‐ or T‐shaped figures in its applications to VLSI layouts. A number of studies have been conducted regarding this problem, but the methods considered in these studies not only have not considered representation of the optimal placement of complicated rectilinear figures but also have not generated permissible neighboring solutions, and searching optimal solutions by search schemes based on these methods is difficult. In order to resolve this problem, this paper proposes multilayered parametric BSG and a placement algorithm using the multilayered parametric BSG. Multilayering allows descriptions representing conditions for nonoverlapping of rectilinear figures simultaneously with constraints of each layer. Parameterization allows multiple solutions represented by the BSG. The proposed method represents complicated rectilinear figures as combinations of a number of element rectangles. When a figure (core cell) with the element rectangles having common parts is the input, it gives the conditions of the multilayered parametric BSG guaranteeing the possibility of generating an optimal solution in terms of the surface area. The practicability of the idea of the proposed method has been verified by testing with several tens of figure inputs by implementing an optimal solution search algorithm based on simulated annealing based on the proposed data structure. © 2004 Wiley Periodicals, Inc. Electron Comm Jpn Pt 3, 87(7): 66–78, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjc.10079
Adaptive Volterra filters using multirate signal processing and their application to identification of loudspeaker systems
Authors: Kinoshita Satoshi , Kajikawa Yoshinobu , Nomura Yasuo
Published: March 2004

The subband adaptive Volterra filter (SBAVF), which can assign the filter length of each subband arbitrarily, is proposed. If the frequency characteristics of a system to be identified are shifted to a certain bandwidth, it is usually not possible to carry out efficient identification by taking account of the shift of the bandwidth in a (full band) adaptive Volterra filter. On the other hand, in the proposed SBAVF, efficient system identification is possible by assigning a longer filter length to the dominant frequency range of the system of interest. When the proposed method is applied to a speaker system, it is shown through simulation results that the error attenuation can be improved from 1.5 dB to 7.5 dB in comparison with the conventional method. © 2004 Wiley Periodicals, Inc. Electron Comm Jpn Pt 3, 87(7): 45–54, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjc.10135
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

This 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

A 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

Previous 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

Malignant 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

Regional 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

We 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

Alterations 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

Neoplastic 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

Extra‐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

Transcriptional 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

Acetylcholinesterase 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

The 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

Inflammatory 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

Long‐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.
Autocrine and paracrine nitric oxide regulate attachment of human osteoclasts
Authors: Yaroslavskiy Beatrice B. , Li Yanan , Ferguson David J.P. , Kalla Sara E. , Oakley Jennifer I. , Blair Harry C.
Published: March 2004

Nitric oxide (NO) can reduce bone loss in chronic bone diseases. NO inhibits or kills osteoclasts, but the mechanism of action of NO in human bone turnover is not clear. To address this, we studied effects of NO on attachment and motility of human osteoclasts on mineralized and tissue culture substrates under defined conditions. Osteoclasts were differentiated in vitro from CD14 selected monocytes in RANKL and CSF‐1, and characterized by cathepsin K expression, tartrate‐resistant acid phosphatase (TRAP) activity, acid secretion, and lacunar resorption. Cell attachment was labeled with monoclonal antibody 23C6, specific for a binding domain of a key osteoclast attachment protein, the CD51/CD61 integrin dimer (αvβ3), with or without cell permeabilization. A ring of integrin attachment during bone degradation delimits an extracellular acid compartment, while αvβ3 forms focal attachments on non‐resorbable substrates. On resorbable substrate but not non‐resorbable substrate, αvβ3 labeling required cell permeabilization, in keeping with the membrane‐matrix apposition that excludes large molecules and allows extracellular acidification. Acid secretion was labeled with the fluorescent weak base indicator lysotracker. NO donors, S‐nitroso‐N‐acetyl penicillamine (SNAP) or sodium nitroprusside (SNP), downmodulated acid secretion simultaneously with cytoskeletal rearrangement, with αvβ3 redistributed to a discontinuous pattern that labeled, on bone substrate, without membrane permeabilization. These effects were reversible, and an inhibitor of NO synthesis, NG‐monomethyl‐L‐arginine (l‐NMMA), increased acid secretion and decreased heterogeneity of attachment structures, showing that NO is an autocrine regulator of attachment. A hydrolysis‐resistant activating cGMP analog 8‐(4‐chlorophenylthio)guanosine‐3′,5′‐cyclic monophosphate replicated effects of NO donors, while an inhibiting analog, 8‐(4‐chlorophenylthio)guanosine‐3′,5′‐cyclic monophosphorothioate, Rp‐isomer, opposed them. On tissue culture or mineralized substrates, NO or cGMP analogs directly regulated motility; after washout cells reattached and survived for days. We conclude that NO is produced by human osteoclasts and regulates acid secretion and cellular motility, in keeping with autocrine and paracrine NO regulation of the resorption cycle. © 2004 Wiley‐Liss, Inc.
Characterizing the new transcription regulator protein p60TRP
Authors: Heese K. , Yamada T. , Akatsu H. , Yamamoto T. , Kosaka K. , Nagai Y. , Sawada T.
Published: March 2004

Active cell death (‘apoptosis’ or ‘programmed cell death’) is essential in the development and homeostasis of multicellular organisms and abnormal inhibition of apoptosis is an indicator of cancer and autoimmune diseases, whereas excessive cell death might be implicated in neurodegenerative disorders such as Alzheimer's disease (AD). Using bioinformatics‐, Western‐blotting‐, yeast‐two‐hybrid‐system‐, polymerase chain reaction (PCR)‐, and fluorescence microscopy‐analyses, we demonstrate here that the neuroprotective protein p60TRP (p60‐transcription‐regulator‐protein) is a basic helix–loop–helix (bHLH) domain‐containing member of a new protein family that interacts with the Ran‐binding‐protein‐5 (RanBP5) and the protein‐phosphatase‐2A (PP2A). The additional findings of its influence on NNT1 and p48ZnF (new‐neurotrophin‐1, p48‐zinc‐finger‐protein)‐signaling and its down‐regulation in the brain of AD subjects point to a possible pivotal role of p60TRP in the control of cellular aging and survival. © 2004 Wiley‐Liss, Inc.
The role of the cytoskeleton in cellular adhesion molecule expression in tumor necrosis factor‐stimulated endothelial cells
Authors: VandenBerg Elizabeth , Reid Maria D. , Edwards John D. , Davis Harold W.
Published: March 2004

Leukocyte infiltration is a hallmark of the atherosclerotic lesion. These cells are captured by cellular adhesion molecules (CAMs), including vascular cell adhesion molecule‐1 (VCAM‐1), intercellular adhesion molecule‐1 (ICAM‐1), platelet‐endothelial cell adhesion molecule (PECAM), and E‐selectin, on endothelial cells (EC). We examined the role of the actin cytoskeleton in tumor necrosis factor‐alpha (TNF‐α)‐induced translocation of CAMs to the cell surface. Human aortic EC were grown on 96‐well plates and an ELISA was used to assess surface expression of the CAMs. TNF‐α increased VCAM‐1, ICAM‐1, and E‐selectin by 4 h but had no affect on the expression of PECAM. A functioning actin cytoskeleton was important for VCAM‐1 and ICAM‐1 expression as both cytochalasin D, an actin filament disruptor, and jasplakinolide, an actin filament stabilizer, attenuated the expression of these CAMs. These compounds were ineffective in altering E‐selectin surface expression. Myosin light chains are phosphorylated in response to TNF‐α and this appears to be regulated by Rho kinase instead of myosin light chain kinase. However, the Rho kinase inhibitor, Y27632, had no affect on TNF‐α‐induced CAM expression. ML‐7, a myosin light chain kinase inhibitor, had a modest inhibitory effect on the translocation of VCAM‐1 but not on ICAM‐1 or E‐selectin. These data suggest that the surface expression of VCAM‐1 and ICAM‐1 is dependent on cycling of the actin cytoskeleton. Nevertheless, modulation of actin filaments via myosin light chain phosphorylation is not necessary. The regulation of E‐selectin surface expression differs from that of the other CAMs. © 2004 Wiley‐Liss, Inc.
Ets proteins in biological control and cancer
Authors: Hsu Tien , Trojanowska Maria , Watson Dennis K.
Published: March 2004

The Ets family consists of a large number of evolutionarily conserved transcription factors, many of which have been implicated in tumor progression. Extensive studies on this family of proteins have focused so far mainly on the biochemical properties and cellular functions of individual factors. Since most of the Ets factors can bind to the core consensus DNA sequence GGAA/T in vitro, it has been a challenge to differentiate redundant from specific functions of various Ets proteins in vivo. Recent findings, however, suggest that such apparent redundancy may in fact be a central component of a network of differentially regulated specific Ets factors, resulting in distinct biological and pathological consequences. The programmed “Ets conversion” appears to play a critical role during tumor progression, especially in control of cellular changes during epithelial–mesenchymal transition and metastasis. Coordination of multiple Ets gene functions also mediates interactions between tumor and stromal cells. As such, these new insights may provide a novel view of the Ets gene family as well as a focal point for studying the complex biological control involved in tumor progression. © 2004 Wiley‐Liss, Inc.
Erratum to: The structure of geodetic blocks with diameter two
Authors: Jingzhong Mao , Lingli Sun
Published: March 2004

In our paper 1 we gave a classification of geodetic blocks of diameter two, but the proof was incorrect. Here we point out this error and give a new result about constructing geodetic blocks of diameter two. © 2004 Wiley Periodicals, Inc. J Graph Theory 46 : 79–80, 2004