bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of FRA6E and its potential role in autosomal recessive juvenile parkinsonism and ovarian cancer
Authors: Denison Stacy R. , Callahan Gwen , Becker Nicole A. , Phillips Leslie A. , Smith David I. 
Published: July 2003

AbstractCharacterization of FRA6E (6q26), the third most frequently observed common fragile site (CFS) in the human population, determined that aphidicolin‐induced instability at FRA6E extends over a very large region (3.6 Mb). Sequence analysis identified eight genes (IGF2R, SLC22A1, SLC22A2, SLC22A3, PLG, LPA, MAP3K4, and PARK2) as mapping within the large FRA6E region. PARK2, the gene associated with autosomal recessive juvenile parkinsonism (ARJP), accounts for more than half of the CFS. Homozygous deletions and large heterozygous deletions have been observed in PARK2 in ARJP patients. RT‐PCR analysis of the eight genes localizing to FRA6E indicated that 50% of the genes, including PARK2, were down‐regulated in one or more of the primary ovarian tumors analyzed. PARK2 expression was down‐regulated in 60.0% of the primary ovarian tumors analyzed. Additionally, we found tumor‐specific alternative transcripts of PARK2. Loss of heterozygosity analysis of primary ovarian tumors by use of polymorphic markers in the 6q26 region demonstrated 72% LOH in the center of the PARK2 gene, the highest of any of the markers tested. FRA6E shares many similarities with FRA3B (3p14.2) and FRA16D (16q23.2) in representing a large region of genomic instability and containing an extremely large gene that may play a role in the development of ovarian and many other cancers. © 2003 Wiley‐Liss, Inc.
Aneuploidy in oncocytic lesions of the thyroid gland: Diffuse accumulation of mitochondria within the cell is associated with trisomy 7 and progressive numerical chromosomal alterations
Authors: Dettori Tinuccia , Frau Daniela V. , Lai Maria L. , Mariotti Stefano , Uccheddu Alessandro , Daniele Giovanni M. , Tallini Giovanni , Faa Gavino , Vanni Roberta 
Published: July 2003

AbstractOncocytic cells are characterized by a greatly increased number of mitochondria that distend the cell cytoplasm and result in a distinctive granular appearance of the cell on conventional histology sections. Oncocytes are frequently found in metabolically active human tissues including the thyroid gland, and, as a general rule, when their proportion in a thyroid tumor is greater than 75% the tumor is referred to as oncocytic (Hürthle cell) adenoma or carcinoma. Such tumors represent a subset of thyroid lesions, and recently, both interphase fluorescence in situ hybridization (FISH) and comparative genomic hybridization (CGH) studies reported that they may show aneuploidy, with widespread numerical chromosomal alterations. In contrast, very few cases have been studied by conventional cytogenetic analysis. Whether the cells with chromosomal changes are the same as those with mitochondrial accumulation or whether lesions only partially composed of oncocytic cells also have cytogenetic alterations is unclear. To investigate the relationship between acquisition of the oncocytic phenotype and numerical chromosomal changes, we analyzed a random selection of thyroid lesions with (18 cases) and without (11 cases) morphological evidence of oncocytic differentiation. Lesions with oncocytes included hyperplastic nodules, adenomas, Hürthle cell tumors, and papillary carcinomas with lymphocytic stroma (Whartin‐like tumors of the thyroid). Karyotypic changes were analyzed by cytogenetic analysis, FISH, or CGH, and the results were compared with in situ analysis of mitochondrial accumulation by immunofluorescence. A striking correlation between the presence of oncocytes and the presence of aneuploid katyotypes was seen in the oncocytic follicular thyroid nodules, but not in the oncocytic papillary tumors. Structural chromosome changes or normal karyotypes were observed in the lesions lacking oncocytic features. Extending the FICTION technique to the evaluation of a cytoplasmic antigen (mitochondrial membrane antigen), we pursued the simultaneous visualization of both mitochondrial increase and numerical chromosomal alterations, and showed that oncocytes of follicular lesions are prone to become aneuploid. Our data support the contention that follicular tumors composed of oncocytes should be regarded as a distinct subset. © 2003 Wiley‐Liss, Inc.
By‐products of immunoglobulin somatic hypermutation
Authors: Bemark Mats , Neuberger Michael S. 
Published: July 2003

AbstractThe antigen receptor loci are the only loci in humans to undergo programmed somatic gene modification. Although aberrant V(D)J integration and class switch recombination can both give rise to chromosomal translocations, a role for somatic hypermutation in such genomic rearrangements has been suggested but is less clearly established. To characterize the types of by‐products of somatic hypermutation, we analyzed aberrant rearrangements involving the immunoglobulin loci in a human B‐cell line (Ramos) that performs Ig V gene hypermutation constitutively during culture. Single‐nucleotide substitutions account for 95% of the mutational events in the VH gene, with small deletions and duplications accounting for most of the remaining mutations. However, larger genetic alterations can be detected at low frequency, accounting for 0.5% of VH‐inactivating mutations. Examples include a large (13 kb) deletion, which entirely removes the expressed VH gene; a 3‐kb deletion extending from the functional VHDJH into an upstream VH (generating a hybrid VHDJH gene reminiscent of VH replacement); and an ectopic insertion into the VH from chromosome 1. The results support the proposal that aberrant antibody hypermutation can lead to gross genomic alterations but indicate that such events are rare. © 2003 Wiley‐Liss, Inc.
Synovial fibroblasts and synovial macrophages from patients with rheumatoid arthritis and other inflammatory joint diseases show chromosomal aberrations
Authors: Kinne Raimund W. , Kunisch Elke , Beensen Volkmar , Zimmermann Thomas , Emmrich Frank , Petrow Peter , Lungershausen Wolfgang , Hein Gert , Braun Rudolf K. , Foerster Martin , Kroegel Claus , Winter Rando , Liesaus Eckehard , Fuhrmann Renée A. , Roth Andreas , Claussen Uwe , Liehr Thomas 
Published: July 2003

AbstractChromosomal aberrations were investigated in nuclei extracted from synovial tissue and first‐passage synovial fibroblasts (P‐1 SFB, 98% enrichment) or macrophages (P‐1 Mϕ) from patients with rheumatoid arthritis (n = 10). The findings were compared with those in other rheumatic diseases (osteoarthritis, n = 14; reactive arthritis, n = 1), as well as with those in chronic obstructive pulmonary disease (n = 8). Controls were paired peripheral blood lymphocytes from arthritic patients, synovial tissue or SFB/Mϕ from joint trauma/normals (n = 9), and peripheral blood monocytes from normal donors (n = 10). GTG banding of metaphase chromosomes and interphase fluorescence in situ hybridization with centromere‐specific probes were used. Comparable chromosomal aberrations were observed in synovial tissue and P‐1 SFB of patients with rheumatoid arthritis, osteoarthritis, and reactive arthritis (polysomy 7 and aneusomies of chromosomes 4, 8, 9, 12, and 18). Notably, aneusomies of chromosomes 4, 6, 7, 8, 9, 11, 12, and/or X were also detected in P‐1 synovial Mϕ from rheumatoid arthritis (90% of the cases), osteoarthritis (93%), and reactive arthritis (1/1), as well as bronchial Mϕ from chronic obstructive pulmonary disease (25%). No aberrations were detected in paired peripheral blood lymphocytes (except for one osteoarthritis case with a karyotype 45,X[10]/46,XX[17]), or in peripheral blood monocytes and synovial tissue of normals/joint trauma. Because Mϕ aberrations were common to chronic joint and pulmonary disease, chronic inflammatory stress may induce chromosomal aberrations with potential functional relevance in local mesenchymal cells and infiltrating leukocytes in an organ‐independent fashion. © 2003 Wiley‐Liss, Inc.
Identification of tissue‐specific genes in nasopharyngeal epithelial tissue and differentially expressed genes in nasopharyngeal carcinoma by suppression subtractive hybridization and cDNA microarray
Authors: Zhang Bicheng , Nie Xinmin , Xiao Bingyi , Xiang Juanjuan , Shen Shourong , Gong Jialei , Zhou Ming , Zhu Shiguo , Zhou Jie , Qian Jun , Lu Hongbin , He Xianfeng , Li Xiaoling , Hu Gengxi , Li Guiyuan 
Published: July 2003

AbstractSuppression subtractive hybridization (SSH) was performed for isolation of tissue‐specific genes in nasopharyngeal epithelial tissue, by use of cDNAs from human adult nasopharyngeal epithelial tissue as tester and mixed cDNAs from esophagus, lung, liver, heart, stomach, spleen, skeletal muscle, kidney, and skin as drivers. Fourteen differentially expressed genes in nasopharyngeal epithelial tissue were obtained. Among these genes, LPLUNC1 and SPLUNC1 were confirmed to be specifically expressed in nasopharyngeal epithelial tissue and the trachea. A novel transcript of SPLUNC1, which we designate NASG, was found. We also combined SSH and cDNA microarray hybridization to identify genes whose expressions were altered in nasopharyngeal carcinoma (NPC). We used NPC cell line HNE1 and primary human embryo nasopharyngeal epithelial cells in one SSH experiment, and NPC biopsies and normal adult nasopharyngeal epithelial tissue in another. Some 1,200 SSH inserts from four subtractive cDNA libraries were arrayed onto nylon membranes by use of robotic printing. Differential gene expression was verified by hybridizing of the membranes with radioactively labeled first‐strand cDNA from NPC cell line HNE1, primary human embryo nasopharyngeal epithelial cells, NPC biopsies, and normal adult nasopharyngeal epithelial tissue. Seventeen differentially expressed genes in NPC were obtained. Among these genes, we identified SPLUNC1 and LPLUNC1 to be down‐expressed in NPC biopsies (34/48, 33/48). © 2003 Wiley‐Liss, Inc.
Mutations and aberrant DNA methylation of the PROX1 gene in hematologic malignancies
Authors: Nagai Hirokazu , Li Yinghua , Hatano Sonoko , Toshihito Ohno , Yuge Masayuki , Ito Etsuro , Utsumi Makoto , Saito Hidehiko , Kinoshita Tomohiro 
Published: July 2003

AbstractThe homeobox gene PROX1 is related to the Drosophila prospero gene, which is expressed in the developing central nervous system and lens‐secreting cone cells. We found that the PROX1 gene had missense and nonsense mutations in 4 of 29 hematologic cell lines analyzed. Decreased mRNA expression was also observed in half of these cell lines by RT‐PCR. The restoration of PROX1 gene expression after treatment with the demethylating agent 5‐aza‐2′‐deoxycytidine, as well as bisulfite sequencing analysis, indicated that gene silencing is caused by DNA hypermethylation at intron 1. Such hypermethylation was also seen in primary lymphomas (56.3%, 18/32) in a tumor‐specific manner. These findings indicate that the profile of the PROX1 gene corresponds to that of a candidate tumor‐suppressor gene. © 2003 Wiley‐Liss, Inc.
Cross‐modal sensory processing in the anterior cingulate and medial prefrontal cortices
Authors: Laurienti Paul J. , Wallace Mark T. , Maldjian Joseph A. , Susi Christina M. , Stein Barry E. , Burdette Jonathan H. 
Published: July 2003

AbstractOne of the principal functions of the nervous system is to synthesize information from multiple sensory channels into a coherent behavioral and perceptual gestalt. A critical feature of this multisensory synthesis is the sorting and coupling of information derived from the same event. One of the singular features of stimuli conveying such information is their contextual or semantic congruence. Illustrating this fact, subjects are typically faster and more accurate when performing tasks that include congruent compared to incongruent cross‐modal stimuli. Using functional magnetic resonance imaging, we demonstrate that activity in select brain areas is sensitive to the contextual congruence among cross‐modal cues and to task difficulty. The anterior cingulate gyrus and adjacent medial prefrontal cortices showed significantly greater activity when visual and auditory stimuli were contextually congruent (i.e., matching) than when they were nonmatching. Although activity in these regions was also dependent on task difficulty, showing decreased activity with decreasing task difficulty, the activity changes associated with stimulus congruence predominated. Hum. Brain Mapping 19:213–223, 2003. © 2003 Wiley‐Liss, Inc.
Aperiodic phase re‐setting in scalp EEG of beta–gamma oscillations by state transitions at alpha–theta rates
Authors: Freeman Walter J. , Burke Brian C. , Holmes Mark D. 
Published: July 2003

AbstractWe evaluated the rapid changes in regional scalp EEG synchronization in normal subjects with spatial and temporal resolution exceeding prior art 10‐fold with a high spatial density array and the Hilbert transform. A curvilinear array of 64 electrodes 3 mm apart extending 18.9 cm across the scalp was used to record EEG at 200/sec. Analytic amplitude (AA) and phase (AP) were calculated at each time step for the 64 traces in the analog pass band of 0.5–120 Hz. AP differences approximated the AP derivative (instantaneous frequency). The AP from unfiltered EEG revealed no reproducible patterns. Filtering was necessary in the β and gamma ranges according to a technique that optimized the correlation of the AP differences with the activity band pass filtered in the alpha range. The sizes of temporal AP differences were usually within ±0.5 radian from the average step corresponding to the center frequency of the pass band. Large AP differences were often synchronized over distances of 6 to 19 cm. An optimal pass band to detect and measure these recurring jumps in AP in the β and γ ranges was found by maximizing the α peak in the cospectrum of the correlation between unfiltered EEG and the band pass AP differences. Synchronized AP jumps recurred in clusters (CAP) at α and theta rates in resting subjects and with EMG. Cortex functions by serial changes in state. The Hilbert transform of EEG from high‐density arrays can visualize these state transitions with high temporal and spatial resolution and should be useful in relating EEG to cognition. Hum. Brain Mapping 19:248–272, 2003. © 2003 Wiley‐Liss, Inc.
Three‐dimensional maximum probability atlas of the human brain, with particular reference to the temporal lobe
Authors: Hammers Alexander , Allom Richard , Koepp Matthias J. , Free Samantha L. , Myers Ralph , Lemieux Louis , Mitchell Tejal N. , Brooks David J. , Duncan John S. 
Published: July 2003

AbstractProbabilistic atlases of neuroanatomy are more representative of population anatomy than single brain atlases. They allow anatomical labeling of the results of group studies in stereotaxic space, automated anatomical labeling of individual brain imaging datasets, and the statistical assessment of normal ranges for structure volumes and extents. No such manually constructed atlas is currently available for the frequently studied group of young adults. We studied 20 normal subjects (10 women, median age 31 years) with high‐resolution magnetic resonance imaging (MRI) scanning. Images were nonuniformity corrected and reoriented along both the anterior‐posterior commissure (AC–PC) line horizontally and the midsagittal plane sagittally. Building on our previous work, we have expanded and refined existing algorithms for the subdivision of MRI datasets into anatomical structures. The resulting algorithm is presented in the Appendix. Forty‐nine structures were interactively defined as three‐dimensional volumes‐of‐interest (VOIs). The resulting 20 individual atlases were spatially transformed (normalized) into standard stereotaxic space, using SPM99 software and the MNI/ICBM 152 template. We evaluated volume data for all structures both in native space and after spatial normalization, and used the normalized superimposed atlases to create a maximum probability map in stereotaxic space, which retains quantitative information regarding inter‐subject variability. Its potential applications range from the automatic labeling of new scans to the detection of anatomical abnormalities in patients. Further data can be extracted from the atlas for the detailed analysis of individual structures. Hum. Brain Mapping 19:224–247,2003. ©2003 Wiley‐Liss,Inc.
Corporate assets as a trust: for whom are corporate officers trustees in insolvency? the role of incentives in maintaining the trust
Authors: Davis Ronald B. 
Published: July 2003

AbstractUncertainty is a constant theme when corporations are in financial distress. Yet any successful restructuring of an insolvent corporation requires numerous stakeholders, including creditors, employees and suppliers, repose some degree of trust in those corporate officers who are trying to continue to operate the firm while restructuring it into a viable entity. This article looks at the issue of the positive and negative incentives that can be generated for corporate officers and directors from both their continuing control of corporate assets and their potential personal liability arising from corporate activity both before and after the corporation became insolvent. The potential role these incentives can play in providing a basis for the trust needed to meet the other governance challenges that arise in a restructuring is reviewed in the context of recent developments in Canada concerning the duties of corporate directors to creditors during insolvency. Also reviewed is the role of directors' insurance and indemnification in altering the incentives' effects on directors' behavior. Finally a critical appraisal is given of the present legal regime's provision for compromise of claims against corporate officers during restructuring, as well as the proposal to amend the law to allow complete exoneration of corporate directors from certain liabilities on insolvency. The article urges caution in altering the effects of incentives that may create the necessary basis for trust in the distressed corporation's officers amongst those stakeholders whose co‐operation is crucial to restructuring. Copyright © 2003 John Wiley & Sons, Ltd.
Changes in immunological and virological parameters in HIV‐1 infected subjects following leukapheresis
Authors: Boulassel M.R. , Spurll G. , Rouleau D. , Tremblay C. , Edwardes M. , Sekaly R.P. , Lalonde R. , Routy J‐P. 
Published: July 2003

AbstractIn order to assess immune responses during HIV‐1 therapeutic immunization, a large number of blood mononuclear cells (PBMC) are needed. Clinical tolerance and safety, as well as changes in immunological and virological parameters, were assessed, following leukapheresis in HIV‐1 infected subjects with CD4+ cell count >200 × 106/l. PBMC were collected using a Fenwal CS3000 cell separator in 29 subjects with mean CD4+ cell counts of 503 × 106/l (range 172–1,119) and viral load of 2.5 log10 copies/ml (range <1.7–5.4). Twenty‐four (83%) subjects were on antiretroviral therapy while 5 (17%) were untreated. The blood volume processed was 7 L over a period of 3 hours. A mean value (± standard error) of 82 ± 26 × 109/l lymphocytes was collected by a single apheresis in a mean volume of 200 ± 1.8 ml, containing 9.0 ± 1.3 × 109/l CD4+ and 10.2 ± 1.3 × 109/l CD8+ cells. The leukapheresis procedures were well tolerated and no immediate or delayed side effects were observed within 90 days of follow‐up. No changes from blood pre‐leukapheresis values were detected for white blood cells, lymphocytes, monocytes, CD8+, CD34+, naive and memory CD4+ cell counts immediately after, 1 h, 7 days, or within 90 days after leukapheresis. However, absolute CD4+ cell counts and percentage significantly increased from pre‐leukapheresis values after 1 h (530 ± 43 vs. 700 ± 75 cell × 106/l; 32.6 ± 1.6 vs. 36.9 ± 1.9%; P < 0.001 for both paired t‐tests) before returning to pre‐leukapheresis levels on day 7. No significant changes in viral load from pre‐leukapheresis levels in treated or untreated subjects were detected at any time points. We conclude that leukapheresis in HIV‐1 infected subjects with CD4+ cell counts >200 × 106/l is safe and induces a transient increase in the absolute and percentage of CD4+ cell count without enhancing viral replication. J. Clin. Apheresis 18:55–60, 2003. © 2003 Wiley‐Liss, Inc.
Clearance of fibrinogen and von Willebrand factor in serial double‐filtration plasmapheresis
Authors: Lin Su‐Mei , Yeh Jiann‐Horng , Lee Chin‐Cheng , Chiu Hou‐Chang 
Published: July 2003

AbstractDouble filtration plasmapheresis (DFP) is a widely used and effective way to clear autoantibodies from plasma. It can, however, transiently alter the hemostatic system and cause a bleeding tendency in some patients. There is limited data on the consecutive effect of serial DFP on the hemostatic system, especially on fibrinogen and von Willebrand factor (vWF) levels. This study measured fibrinogen and vWF serially before and after each session of DFP in 8 patients who received one course of DFP treatment for 3 to 5 consecutive sessions on an alternate‐day basis. In each session of DFP, the clearance rate of fibrinogen and vWF exceeded 63 and 45%, respectively. The final levels of fibrinogen and vWF after a full course of DFP were reduced to 14.3 and 51.2% of baseline level, respectively. No bleeding tendency was observed in any of the 34 DFP sessions. In conclusion, although an obvious decrease in fibrinogen level and the modest decrease in vWF were observed after an intensive course of DFP treatment, the low incidence of clinically important bleeding confirms the hemostasis‐related safety of DFP. J. Clin. Apheresis 18:67–70, 2003. © 2003 Wiley‐Liss, Inc.
Role of splenectomy in patients with refractory or relapsed thrombotic thrombocytopenic purpura
Authors: Aqui Nicole A. , Stein Steven H. , Konkle Barbara A. , Abrams Charles S. , Strobl Frank J. 
Published: July 2003

AbstractThrombotic thrombocytopenic purpura (TTP) was once uniformly fatal. Therapeutic plasma exchange in combination with immunosuppressive and anti‐platelet agents, however, have resulted in improved survival rates of greater than 80% for patients with TTP. In spite of aggressive plasma exchange and adjuvant therapy, a number of TTP patients are refractory to treatment. In addition, up to 40% of TTP patients who initially respond to therapy eventually relapse. Alternative therapies such as splenectomy have been used with varying degrees of success in refractory and relapsing TTP patients. The usefulness of splenectomy in preventing relapse of TTP or treating those patients who are refractory to plasma exchange remains controversial. We present a single institution's experience with 14 patients who underwent splenectomy for refractory (six patients) or relapsed (eight patients) TTP since 1984. In both patient groups, splenectomy induced stable long‐term remissions. Six of six (100%) patients who were refractory to plasma exchange, survived to be discharged from the hospital, apparently free of disease. Four of eight patients (50%) who had a splenectomy for relapsing TTP went into a complete remission and had no further relapses of their disease. Moreover, in relapsing patients who failed to experience long‐term remission, the relapse rate after splenectomy was 0.3 events per patient year compared to 1.0 events per patient year prior to splenectomy. We conclude that splenectomy is a reasonable treatment option for TTP patients refractory to standard plasma exchange therapy or who have experienced multiple and/or complicated relapses. We believe this is the first series that demonstrates efficacy of splenectomy in plasma exchange‐refractory TTP. J. Clin. Apheresis 18:51–54, 2003. © 2003 Wiley‐Liss, Inc.