bluuebunny/crossref_metadata_2025_split huggingface dataset:
Automatic quantification of gene amplification in clinical samples by IQ‐FISH
Authors: Narath R. , Lörch T. , Rudas M. , Ambros P. F. 
Published: December 2003

AbstractBACKGROUNDThe reliable detection and quantification of gene amplifications is crucial to clinical practice. Although there are different detection techniques, the fluorescence in situ hybridization (FISH) method has become highly accepted over past years because it is a reliable, robust, and quick method. Unfortunately, automatic quantification of gene amplification based on fluorescence intensities has not been possible thus far. Because current spot counting methods are reliable only when analyzing low amplification rates, we attempted to establish another method, i.e., to quantify the intensity of different FISH signals using an automatic fluorescence microscopical device on interphase nuclei: interphase quantitative FISH (IQ‐FISH).METHODSWe quantified the fluorescence intensities of the differently labeled FISH probes (MYCN and D2Z) hybridized to three different neuroblastoma cell lines, six peripheral blood (PB) samples, 10 spiked PB samples, and nine neuroblastoma samples using the Metafer4 system (MetaSystems, Altlussheim, Germany). To obtain the MYCN copy number per cell, the ratio between the fluorescence intensities of the MYCN gene and reference sequence (D2Z) was calculated. For automatic analysis of the HER‐2/neu status in tumor cells, labeled FISH probes specific for HER‐2/neu and a chromosome 17–specific probe were hybridized to peripheral blood and tumor specimens and analyzed using the automatic device.RESULTSWhen measuring the fluorescence intensity per cell for both probe pairs (MYCN/D2Z and HER‐2/17p), amplified and non‐amplified cells, showed distinct peaks with only little overlap. Whereas normal cells showed a fluorescence ratio peak for MYCN/D2Z between 200 and 800, cells with MYCN amplification clearly exceeded this ratio value (1000 to 25,000). When mixing a varying number of MYCN amplified cells (range 9–91%) to normal PB, the spiked tumor cells could be identified. Even one neuroblastoma tumor cell in 1000 mononucleated cells could reliably be detected using our device. In neuroblastoma patient samples, non‐amplified cells were distinguished from amplified cells. Automatically and manually counted signals gave matching results in amplified and non‐amplified samples. HER‐2/neu–amplified cells were automatically detected in the breast cancer samples analyzed.CONCLUSIONThe automatic measurement of fluorescence signal intensities not only allows a reliable discrimination between non‐amplified and amplified cells but also exact quantification of amplified sequences. This is the prerequisite for the following applications: detection of amplified cells in the bone marrow and second‐look specimens; comparison between primary and relapse or pre‐ and post‐chemotherapeutic specimens; detection of tumors with focal gene amplification; and quantification of elimination of amplified gene sequences. © 2003 Wiley‐Liss, Inc.
Flow cytometric quantitation of red blood cell vesicles in thalassemia
Authors: Pattanapanyasat Kovit , Noulsri Egarit , Fucharoen Suthat , Lerdwana Surada , Lamchiagdhase Pornvaree , Siritanaratkul Napadol , Webster H. Kyle 
Published: December 2003

AbstractBACKGROUNDThalassemia is a hereditary hemolytic anemia caused by mutations in the globin gene complex. Circulatory disturbances including arterial and venous thrombosis have also been noted in these patients. Aggregability of abnormal RBC and the high level of membrane‐derived microparticles stemming from activated platelets and other blood cells are thought to be responsible for the associated thrombotic risk. Destruction of RBC is also thought to be an important pathophysiological consequence, particularly through the formation of circulating vesicles. To our knowledge, there has been no attempt to quantitatively evaluate the number of RBC vesicles in thalassemia. This prompted us to study the level of RBC vesicles in the peripheral blood of thalassemia patients using quantitative flow cytometry.METHODSWhole blood from each subject was doubly stained for RBC and platelet or annexin V markers, together with the known density TruCount™ beads. RBC vesicles were gated according to their forward/side scatter and RBC marker. Percentage of RBC vesicles and their absolute number were analyzed by flow cytometry.RESULTSOur data indicated that RBC vesicles were annexin V–positive. The number of annexin V–positive events was higher than their intact RBCs. RBC vesicles were present in both normal and thalassemic blood samples, but the numbers of RBC vesicles were significantly higher in thalassemia. Both the percentage and the absolute number of RBC vesicles were especially marked in splenectomized subjects with β‐thalassemia/Hemoglobin E. When clinical and hematological indices were compared with RBC vesicles, there was an inverse relationship between the degree of severity in thalassemia patients and the number of RBC vesicles.CONCLUSIONFlow cytometric quantitation of RBC vesicles is simple, reliable and may offer new insights in to study of the relationship between defective hemoglobin synthesis, RBC perturbation and pathophysiological complications in thalassemia. © 2003 Wiley‐Liss, Inc.
Cytologic diagnosis of ossifying fibromyxoid tumor of soft tissue: A case report
Authors: Mohanty Sambit K. , Srinivasan Radhika , Rajwanshi Arvind , Vasishta Rakesh Kumar , Vignesh P.S. 
Published: December 2003

AbstractOssifying fibromyxoid tumor (OFMT) of soft tissue is an uncommon, recently described neoplasm. It is usually, but not universally, a benign neoplasm and cases of metastatic so‐called “malignant OFMT” have been reported. Although the histopathologic features of OFMT are well characterized, the same is not entirely true so far as the cytology literature is concerned. There are only three cytologic descriptions of OFMT to date to the best of our knowledge. A 62‐year‐old woman presented with a subcutaneous well‐circumscribed nodular soft tissue mass at the upper end of the shoulder. X‐ray and computed tomography revealed an incomplete shell of calcification surrounding the nodular mass along with foci of ossification within it. Fine‐needle aspiration (FNA) cytology showed round to polygonal to spindle shaped neoplastic cells arranged in clusters, cords, and small aggregates and lying discretely in a mucoid background. Some osteoid‐like material was also seen. The tumor was completely excised and histopathologic examination confirmed the diagnosis of OFMT. OFMT should be considered as a possibility in FNA cytology of myxoid soft tissue tumor especially with radiologic evidence of ossification. Diagn. Cytopathol. 2004;30:41–45. © 2004 Wiley‐Liss, Inc.
Paratesticular congenital malignant rhabdoid tumor diagnosed by fine‐needle aspiration cytology. A case report
Authors: Salamanca Javier , Rodríguez‐Peralto José Luis , Azorín Daniel , Ballestín Claudio , De Agustín Pedro 
Published: December 2003

AbstractWe report the FNA features of a congenital malignant extrarenal rhabdoid tumor (MERT) located in the right paratesticular area of a newborn full‐term boy (39 wk gestation), with disseminated metastases in the liver and right parietal region. The diagnosis was suggested two days after birth by fine‐needle aspiration biopsy (FNAB) of the parietal mass, which demonstrated an atypical large cell proliferation with vesicular nuclei, prominent nucleoli, and abundant cytoplasm exhibiting paranuclear dense inclusions. The diagnosis was confirmed by histopathologic and immunohistochemical examination of the primary paratesticular tumor. To the best of our knowledge, this is the third MERT reported in the paratesticular region, one of the few congenital extrarenal non‐central nervous system cases, and the third congenital case (renal or extrarenal) primarily diagnosed by FNAB. We emphasize the characteristic cytologic features of a congenital rhabdoid tumor, which must be known by pathologists because of the clinical and prognostic implications. Diagn. Cytopathol. 2004;30:46–50. © 2004 Wiley‐Liss, Inc.
Monophasic synovial sarcoma: A cytologic spectrum
Authors: Ewing C. Alexander , Zakowski Maureen F. , Lin Oscar 
Published: December 2003

AbstractSynovial sarcoma (SS) is a high‐grade sarcoma that can be diagnosed in cytology with certainty only when it presents with a biphasic pattern. Monophasic SS (MSS), however, is a diagnostic consideration when a uniform spindle cell population is present. The purpose of this study was to evaluate a series of cytologic cases of MSS and its cytologic presentation. Twenty‐one FNAs of histologically confirmed MSS were reviewed. Specimens consisted of tissue fragments and single cells containing scant granular cytoplasm, medium‐sized nuclei, and coarse chromatin. A monotonous spindle pattern with comma‐shaped nuclei was present in 5 cases. Sixteen cases contained oval and spindled nuclei. Eight of these specimens contained round nuclei, and 5 of these cases showed prominent nucleoli and cohesive clusters, reminiscent of biphasic SS. We conclude that a spectrum of cytologic findings can be seen in MSS, including a secondary population of cells with morphology usually typical of biphasic SS. Diagn. Cytopathol. 2004;30:19–23. © 2004 Wiley‐Liss, Inc.
Primary pulmonary adenoid cystic carcinoma: Report of a case diagnosed by fine‐needle aspiration cytology
Authors: Qiu Suimin , Nampoothiri Madhavan M. , Zaharopoulos Paul , Logroño Roberto 
Published: December 2003

AbstractAdenoid cystic carcinoma of the lower respiratory tract is an uncommon tumor that can arise in the mainstem bronchus and often presents as an endobronchial mass lesion causing bronchial obstruction with post obstructive atelectasis and pneumonia. Exfoliative cytology is seldom useful in the diagnosis of primary bronchial adenoid cystic carcinoma, because these neoplasms usually have a submucosal location with often intact mucosa. Since most endobronchial adenoid cystic carcinomas are endoscopically visible, bronchoscope‐guided fine‐needle aspiration constitutes an excellent approach to establish a pathologic diagnosis. The fine‐needle aspiration cytology of primary pulmonary adenoid cystic carcinoma has been rarely described. We report a case of primary adenoid cystic carcinoma of the lung having characteristic cytologic features and correlate with computed tomography, bronchoscopic, and histological findings. Bronchoscope‐guided aspiration cytology provided a conclusive diagnosis of adenoid cystic carcinoma, which was further corroborated by histology in the pneumonectomy specimen. Diagn. Cytopathol. 2004;30:51–56. © 2004 Wiley‐Liss, Inc.
Developmental changes in eyeblink conditioning and simple spike activity in the cerebellar cortex
Authors: Nicholson Daniel A. , Freeman John H. 
Published: December 2003

AbstractThe activity of neurons in the cerebellum exhibits learning‐related changes during eyeblink conditioning in adult mammals. The induction and preservation of learning‐related changes in cerebellar neuronal activity in developing rats may be affected by the level of maturity in cerebellar feedback to its brainstem afferents, including the inferior olive. Developmental changes in cerebellar plasticity were examined by recording the activity of Purkinje cells in eye regions of cerebellar cortical lobule HVI (lobulus simplex) in infant rats during eyeblink conditioning. The percentage and amplitude of eyeblink conditioned responses increased as a function of age. Analyses of Purkinje cell simple spike activity revealed developmental increases in the number of units that exhibited stimulus‐evoked and learning‐related changes in activity. Moreover, the magnitude of these changes exhibited a substantial age‐related increase. The results support the view that the emergence of learning‐specific cerebellar plasticity and the ontogeny of eyeblink conditioning are influenced by developmental changes in the synaptic interactions within brainstem–cerebellum circuits. © 2003 Wiley Periodicals, Inc. Dev Psychobiol 44: 45–57, 2004.
The aims and accomplishments of comparative psychology
Authors: Lickliter Robert 
Published: December 2003

AbstractGreenberg, Partridge, Weiss, and Pisula propose a new perspective of comparative psychology, based in large part on an anagenetic and dynamic systems approach to the development and evolution of behavior. Their view appreciates the probabilistic nature of behavioral development and promotes the value of an integrative levels concept for generating testable hypothesis regarding the complex relationship between biology, context, and developmental history underlying behavioral and psychological functioning. However, the authors fail to represent the full scope of contemporary comparative psychology by overlooking several core aims of the field, including (a) the use of animal models to shed light on human behavior and development and (b) understanding the role of behavior as a leading edge in the evolutionary process. © 2003 Wiley Periodicals, Inc. Dev Psychobiol 44: 26–30, 2004.
Finding large‐scale spatial trends in massive, global, environmental datasets
Authors: Johannesson G. , Cressie N. 
Published: December 2003

AbstractAs technology progresses, the availability of massive environmental data with global spatial coverage has become quite common. An example of such data is total column ozone (TCO) remotely sensed from a satellite. In their raw form, these data are often spatially (and temporally) dense, but irregular. The problem considered here is one of detecting a large‐scale spatial trend at a given time point (actually, in a given time interval). We propose a sequential aggregation method, producing different levels of coarser (spatial) resolution data and, at the same time, preserving both the local information content and the locations of the raw data. In estimating the large‐scale trend, we consider different types of smooth spatial trend surfaces on the sphere, all linear combinations of smooth basis functions and satisfying the topological constraints imposed by the sphere. These include trend surfaces based on tensor products of splines, spherical harmonic basis functions, smoothing spherical splines and a new trend surface that we call fixed‐rank smoothing (FRS). The FRS trend surfaces can be based on any set of smooth basis functions on the sphere and are estimated via penalized weighted‐least‐squares regression (ridge regression) using a data‐adaptive penalty term. In comparing the various trend surfaces considered, we look at data fidelity, trend‐surface consistency when fitted to data at different resolutions, and small‐ and large‐scale spatial behavior of the resulting detrended fine‐resolution data. An application to the TCO data reveals that the large‐scale spatial trend can be detected and effectively estimated using coarse‐resolution data. The FRS trend surfaces are seen to achieve better data fidelity than other trend surfaces considered, and, in terms of trend‐surface consistency and small‐ and large‐scale residual behavior, FRS is seen to have as good, and sometimes better, performance. Copyright © 2003 John Wiley & Sons, Ltd.
A novel gene, FGA7, is fused to RUNX1/AML1 in a t(4;21)(q28;q22) in a patient with T‐cell acute lymphoblastic leukemia
Authors: Mikhail Fady M. , Coignet Lionel , Hatem Nadia , Mourad Zeinab I. , Farawela Hala M. , Kaffash Dalal M. El , Farahat Nahla , Nucifora Giuseppina 
Published: December 2003

AbstractAML1 is among the most frequent targets of chromosomal rearrangements in human leukemias. We report here the molecular analysis of a t(4;21)(q28;q22) that has disrupted AML1 in a patient with de novo T‐cell acute lymphoblastic leukemia. By using 3′‐RACE analysis, we show that this rearrangement results in the fusion of a novel gene immediately downstream of exon 5 or exon 6 of AML1, indicating that the AML1 breakpoint lies in intron 6 and that alternative fusion splice variants are generated. The sequence of the novel gene, located at 4q28, does not have any significant homology with any of the known genes in the human GenBank DNA database. However, the first 118 bases are identical to a part of a human ovarian EST. Also, its high homology with mouse and rat sequences suggests that this sequence most probably represents a part of a novel gene, which we named FGA7 (Fused Gene 7 to AML1). Following the AML1 open reading frame, the FGA7 sequence encodes an unknown protein of 27 amino acids. We isolated three bacterial artificial chromosome (BAC) clones that contain the FGA7 sequence and confirmed the breakpoint of the gene on the patient's metaphase spreads by fluorescence in situ hybridization using these BACs as probes. RT‐PCR and Northern blot analyses revealed that FGA7 is expressed in ovarian and skeletal muscle tissues. The predicted AML1‐FGA7 chimeric proteins contained a limited number of residues fused to AML1 in a situation similar to that reported for the AML1‐EAP fusion that is a product of t(3;21). It is possible that the expression of a constitutively shortened AML1 could compete with full‐length AML1 and act as a dominant negative inhibitor of the promoters that the core binding factor activates. © 2004 Wiley‐Liss, Inc.
Distinct MDM2 and P14ARF expression and centrosome amplification in well‐differentiated liposarcomas
Authors: Perucca‐Lostanlen D. , Rostagno P. , Grosgeorge J. , Marcié S. , Gaudray P. , Turc‐Carel C. 
Published: December 2003

AbstractWell‐differentiated liposarcomas (WDLs) are common soft‐tissue tumors in adults. They are characterized by large marker chromosomes and/or ring chromosomes containing 12q‐derived sequences in which MDM2 is consistently amplified. WDLs are subdivided into two subtypes according to their karyotype. Type D cells exhibit a near‐diploid karyotype, with very few or no chromosome changes. Type H cells exhibit a near‐tetraploid karyotype and many structural changes. Expression of P14ARF, MDM2, and TP53 proteins was assayed in the two WDL subtypes to establish whether distinct expression profiles correlated with cell ploidy. Although a transcriptionally functional TP53 was present in most tumors independent of their karyotype, type H cells were characterized by high levels of P14ARF and MDM2 proteins. Although amplified within similar chromosome markers in type D tumors, MDM2 did not appear to be overexpressed. In addition, it was present as a C‐terminal truncated protein, indicative of alternatively spliced variants of MDM2 mRNA. As the existence of karyotypically distinct tumors could result from alterations of the mitotic machinery, we investigated the centrosome behavior in the two WDL subtypes. Centrosome amplification occurred in WDL tumors types H and D independent of their ploidy status. Moreover, no functional centrosome difference was found between the two tumor subtypes. © 2003 Wiley‐Liss, Inc.
Germ‐line ATM gene alterations are associated with susceptibility to sporadic T‐cell acute lymphoblastic leukemia in children
Authors: Liberzon Ella , Avigad Smadar , Stark Batia , Zilberstein Julia , Freedman Laurence , Gorfine Malka , Gavriel Herzel , Cohen Ian J. , Goshen Yacov , Yaniv Isaac , Zaizov Rina 
Published: December 2003

AbstractA major feature of ataxia‐telangiectasia (A‐T) is an increased risk of cancer, particularly of lymphoid malignancies. We studied ATM gene involvement in leukemic cells derived from 39 pediatric T‐cell acute lymphoblastic leukemias (ALLs). Two types of sequence changes—truncating and missense—were identified in 8 T‐cell ALL samples: 3 truncating changes, all previously identified in A‐T (R35X, −30del215, 2284delCT), and 3 missense variants (V410A, F582L, F1463C) were found, none associated with loss of heterozygosity (LOH). In all patients studied, the mutation was present in the germ‐line. A‐T carriers, defined by the finding of truncating mutations, were found to be 12.9 times more frequent than in the normal population (P = 0.004). A normally ethnically matched population was screened for the 3 missense variants, and their frequency was significantly more prevalent (4.9‐fold excess) than in the normal population (P = 0.03). Our data suggest there is some evidence of an association between missense alterations in the ATM gene and T‐cell ALL. A significant difference in the mean age at diagnosis of T‐cell ALL was noted between patients harboring an ATM sequence change and those with no change, 5.4 years and 9.7 years, respectively (P = 0.001). No ATM alterations were identified in relapse samples, indicating that ATM does not play a role in disease progression. The high prevalence of germ‐line truncating and missense ATM gene alterations among children with sporadic T‐cell ALL suggests an association with susceptibility to T‐cell acute leukemia and supports the model of predisposition to cancer in A‐T heterozygotes. © 2003 Wiley‐Liss, Inc.
Amplification and overexpression of the IGF2 regulator PLAG1 in hepatoblastoma
Authors: Zatkova Andrea , Rouillard Jean‐Marie , Hartmann Wolfgang , Lamb Barbara J. , Kuick Rork , Eckart Markus , von Schweinitz Dietrich , Koch Arend , Fonatsch Christa , Pietsch Torsten , Hanash Sam M. , Wimmer Katharina 
Published: December 2003

AbstractThere is evidence that 8q amplification is associated with poor prognosis in hepatoblastoma. A previous comparative genomic hybridization analysis identified a critical region in chromosomal bands 8q11.2–q13. Using restriction landmark genomic scanning in combination with a virtual genome scan, we showed that this region is delineated by sequences within contig NT_008183 of chromosomal subbands 8q11.22–q11.23. A real‐time PCR–based genomic copy number assay of 20 hepatoblastomas revealed gain or amplification in this critical chromosomal region in eight tumors. The expression of four genes and expressed sequence tags (ESTs) within this newly defined region was assayed by real‐time reverse transcriptase polymerase chain reaction (RT‐PCR) in four tumors with and six tumors without gain or amplification. The PLAG1 oncogene was found to be highly expressed in all but one tumor compared to normal liver tissue. Furthermore, quantitative RT‐PCR revealed that the expression level of the developmentally regulated transcription factor PLAG1 was 3–12 times greater in hepatoblastoma tumors and cell lines compared to age‐matched normal liver and comparable to the expression in fetal liver tissue. PLAG1 has been shown be a transcriptional activator of IGF2 in other tumor types. Using luciferase reporter assays, we demonstrated that PLAG1 transactivates transcription from the embryonic IGF2 promoter P3, also in hepatoblastoma cell lines. Thus, our results provide evidence that PLAG1 overexpression may be responsible for the frequently observed up‐regulation of IGF2 in hepatoblastoma and therefore may be implicated in the molecular pathogenesis of this childhood neoplasia. © 2003 Wiley‐Liss, Inc.