bluuebunny/crossref_metadata_2025_split huggingface dataset:
COX-2 expression in ampullary carcinoma: correlation with angiogenesis process and clinicopathological variables
Authors: Perrone G , Santini D , Verzì A , Vincenzi B , Borzomati D , Vecchio F , Coppola R , Antinori A , Magistrelli P , Tonini G , Rabitti C 
Published: February 2006

Background:There is evidence that the anti-neoplastic effect of non-steroidal anti-inflammatory drugs is attributable to cyclooxygenase-2 (COX-2) inhibition, but the exact mechanisms whereby COX-2 can promote tumour cell growth remain unclear. One hypothesis is the stimulation of tumour angiogenesis by the products of COX-2 activity. To data, there have been few clinicopathological studies on COX-2 expression in human ampullary carcinoma and no data have been reported about its relation with tumour angiogenesis.Objective:To investigate by immunohistochemistry the expression of COX-2 and the angiogenesis process in a series of primary untreated ampullary carcinomas.Methods:Tissue samples from 40 archival ampullary carcinomas were analysed for COX-2, vascular endothelial growth factor (VEGF), and an endothelial cell marker von Willebrand factor (vWF) by immunohistochemistry, using specific antibodies.Results:COX-2 expression was detected in 39 tissue samples (97.5%), of which two (5%) were graded as weak, 26 (65%) as moderate, and 11 (27.5%) as strong. Only one lesion (2.5%) was negative for COX-2 expression. VEGF expression was detected in 36 tissue samples (90%). A significant positive correlation was found between COX-2 and VEGF expression. No statistic correlation was found between COX-2 expression and microvessel density.Conclusions:COX-2 is highly expressed in ampullary carcinomas. This suggests an involvement of the COX-2 pathway in ampullary tumour associated angiogenesis, providing a rationale for targeting COX-2 in the treatment of ampullary cancer.
Role of Epstein-Barr virus DNA measurement in plasma in the clinical management of nasopharyngeal carcinoma in a low risk area
Authors: Kalpoe J S , Douwes Dekker P B , van Krieken J H J M , Baatenburg de Jong R J , Kroes A C M 
Published: February 2006

Objective:To evaluate the role of quantitative measurement of Epstein-Barr virus (EBV) DNA in the clinical management of nasopharyngeal carcinoma (NPC) in a low tumour risk area (western Europe).Methods:22 consecutive Dutch NPC patients (11 europid) were studied. EBV DNA load in pretreatment and post-treatment plasma samples was determined. Three patients were also sampled at frequent intervals during treatment. RNA in situ hybridisation for the detection of EBV encoded RNAs (EBERs) was carried out on tumour biopsies of all cases.Results:All patients with EBER positive NPC (20/22) showed a positive EBV DNA load in plasma at the time of diagnosis (median EBV DNA level, 4.1 log10copies/ml). Patients with EBER negative NPC had no detectable EBV DNA in plasma. After treatment, complete remission was achieved in all cases and concurrently EBV DNA in plasma became undetectable in all patients. In the three longitudinally evaluated cases, EBV DNA load gradually declined towards undetectable levels within three weeks after start of treatment. Two patients developed a distant metastasis with concomitant increases in EBV viral load. In addition, one EBER positive patient developed an EBER negative metastasis in the neck during follow up and in this case EBV DNA load remained undetectable at the time of recurrence.Conclusions:Plasma EBV DNA load measurement appears to be useful in a low tumour risk area. However, development of local recurrences may not always coincide with raised levels of EBV DNA.
High-frequency promoter hypermethylation of the deleted in liver cancer-1 gene in multiple myeloma
Authors: Song Y-F , Xu R , Zhang X-H , Chen B-B , Chen Q , Chen Y-M , Xie Y 
Published: February 2006

Background:Deleted in liver cancer-1 (DLC-1) is a tumour suppressor gene that is inactive in liver carcinogenesis. It encodes a ρ-guanosine triphosphatase-activating protein (ρ-GAP) and maps to one of the deleted regions (8p21.3–22). Little is known, however, about the methylation status of theDLC-1promoter in myeloma cells.Aim:To identify whether methylation ofDLC-1was associated in pathogenesis of multiple myeloma.Methods:Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect DLC-1 transcripts in RPMI 8226, U266, OPM-2 and XG-2 cell lines. The methylation status was determined by methylation-specific PCR followed by bisulphite DNA sequencing in these four cell lines and in the bone marrow of 14 patients with multiple myeloma and 4 normal patients. DLC-1 mRNA expression in cells with or without treatment with 5-aza-deoxycytidine (5-aza-CdR) or trichostatin A (TSA) was investigated by real-time RT-PCR.Results:RPMI 8226 and U266 showed complete methylation and XG-2 showed partial methylation.DLC-1was expressed only in OPM-2 cell lines that showed no methylation.DLC-1methylation was shown in 11 of 14 (78%) patients with multiple myeloma and none of the normal controls. The exposure of cell lines to 5-aza-CdR or TSA resulted in the up regulation ofDLC-1gene expression.Conclusions:DLC-1methylation is often present in multiple myeloma and has a key role inDLC-1silencing.
Differential expression and distribution of epithelial adhesion molecules in non-small cell lung cancer and normal bronchus
Authors: Boelens M C , van den Berg A , Vogelzang I , Wesseling J , Postma D S , Timens W , Groen H J M 
Published: February 2006

Background:Changes in epithelial cell interactions have been implicated in carcinogenesis, tumour invasion and metastasis.Aim:To screen for altered expression of epithelial adhesion genes in lung cancer development.Methods:Gene expression profiles were assessed with cDNA expression arrays in eight non-small cell lung cancer (NSCLC) and eight normal bronchi obtained from the same patient. Immunohistochemistry (IHC) and RNA in situ hybridisation (ISH) were used to confirm the most prominently expressed adhesion molecules and to investigate their distribution at protein and mRNA levels.Results:43 differentially expressed cancer-related genes were identified in adenocarcinoma, squamous cell carcinoma (SCC) and normal bronchus. Five of these genes are related to epithelial adhesion—that is, integrin α3 (ITGA3), integrin β4 (ITGB4), desmoplakin I and II (DSP), plakoglobin, and desmocollin 3 (DSC3). ITGA3 and ITGB4, showing predominantly cell–matrix staining, were up regulated in adenocarcinoma and SCC, respectively. ITGB4 also showed strong staining in SCC with IHC and ISH. Components of the desmosome adhesion complex DSP, plakoglobin and DSC3 were strongly up regulated in SCC and showed a distinct cell–cell staining pattern. DSP and plakoglobin were predominantly present at central, more differentiated tumour cells, whereas DSC3 showed a stronger staining in the peripheral basal cells of SCC tumour areas.Conclusions:Lack of cellular adhesion may have an important role in the metastatic potency of a primary tumour. A possible association of strong presence and normal-distributed desmosomal molecules in SCC with the less frequent and late pattern of metastasis in SCC as compared with adenocarcinoma is suggested.
Relevance of postmortem radiology to the diagnosis of fatal cerebral gas embolism from compressed air diving
Authors: Cole A J , Griffiths D , Lavender S , Summers P , Rich K 
Published: February 2006

Aims:To test the hypothesis that artefact caused by postmortem off-gassing is at least partly responsible for the presence of gas within the vascular system and tissues of the cadaver following death associated with compressed air diving.Methods:Controlled experiment sacrificing sheep after a period of simulated diving in a hyperbaric chamber and carrying out sequential postmortem computed tomography (CT) on the cadavers.Results:All the subject sheep developed significant quantities of gas in the vascular system within 24 hours, as demonstrated by CT and necropsy, while the control animals did not.Conclusions:The presence of gas in the vascular system of human cadavers following diving associated fatalities is to be expected, and is not necessarily connected with gas embolism following pulmonary barotrauma, as has previously been claimed.
Do we need to measure total serum IgA to exclude IgA deficiency in coeliac disease?
Authors: Sinclair D , Saas M , Turk A , Goble M , Kerr D 
Published: February 2006

Background:Screening for IgA deficiency in patients with coeliac disease is essential because of the increased incidence of IgA deficiency associated with the disease, which usually relies on the estimation of IgA levels in each case.Aim:To devise a method of excluding IgA deficiency without measuring total serum IgA in each case.Materials and methods:The optical density readings on enzyme-linked immunosorbent assay (ELISA) of 608 routine samples received for tissue transglutaminase (TTG) antibody testing for coeliac disease were compared with their total IgA concentrations. Dilution experiments were also carried out to ensure linear relationships between optical density on ELISA and IgA concentrations and to compare the sensitivities for TTG and endomysium antibodies in TTG-positive samples.Results and discussion:A clear relationship was shown between total IgA concentration and TTG optical density readings by ELISA. To ensure a positive TTG result if antibodies are present, it was possible to recommend an optical density level above which all samples have sufficient IgA. Samples with optical density <0.05 should be investigated further by estimating total IgA and, if low, samples should be subjected to immunofluorescence microscopy testing for IgA and IgG endomysium antibodies.Conclusions:An easier, more cost-effective and practical way of excluding IgA deficiency in the investigation on coeliac disease is reported.
Hypoplasia and neuronal immaturity of the hypoglossal nucleus in sudden infant death
Authors: Ottaviani G , Matturri L , Mingrone R , Lavezzi A M 
Published: February 2006

Objective:To report the case of five month old female baby with a history of episodes of gastro-oesophageal reflux and pneumonia. Her sudden death offered a unique insight into the possible role of delayed neuronal maturation and hypoplasia of the hypoglossal nucleus in representing a likely morphological substrate of sudden death.Methods:Morphometric analysis was carried out with an Image-Pro Plus Image analyser (Media Cybernetics) on both sides of the brain stem.Results:Hypoplasia and neuronal immaturity of the hypoglossal nucleus were demonstrated, accompanied by hypoplasia of the arcuate nucleus.Conclusions:Much attention should be paid to the possible role of the hypoglossal nucleus in determining a lethal outcome in infancy through impairment of deglutition and subsequent recurrent episodes of pneumonia, and as a necropsy finding.
THE INFLUENCE OF SPECIES' NUMBER AND THE DENSITY OF VACANT SITES ON THE DEFENSIVE ALLIANCE
Authors: HE MINGFENG , CAI YU , WANG ZHIRUI , PAN QIU-HUI 
Published: February 2006

The multi-species ecological system with cyclic dominance and vacant sites is studied. The theme is the forming problem of species' defensive alliances in the corresponding systems. György Szabó and Gustavo Arial Sznaider have discussed the forming problem of species' defensive alliance in Phys. Rev. E69, 031911 (2004). Now, this problem is discussed in depth. The following conclusions are obtained: Firstly, the necessary and sufficient condition of forming defensive alliances is that the number of species is even. Secondly, in the condition where the number of species is an even number, for any density of vacant sites, there is three forms of defensive alliance as follow: • Deadlock — the habitats of specie's individuals in each alliance interweave together. • Relative preponderance — the different of the number of species' individuals between the two defensive alliances keeps steadily. • Absolute preponderance — the different of the number of species' individuals between the two defensive alliances enlarges continuously. This paper discusses the relations between the number of species and the forming of the defensive alliances, and shows the corresponding three statistical distributions of discrete density of vacant sites when there are four species.
MACRODYNAMIC COOPERATIVE COMPLEXITY OF BIOSYSTEMS
Authors: LERNER VLADIMIR S. 
Published: February 2006

The introduced dynamic macrocomplexity (MC) is an indicator of the phenomena and parameters of the cooperative dynamic process in a complex system with the macrolevel's dynamics and random microlevel's stochastics. The MC, arising from the unification (or decomposition) of the system's elements, is defined by the information measure, allowing for both analytical formulation and computer evaluation. The MC cooperative mechanism is analyzed using the minimax variation principle of Information Macrodynamics (IMD). When applied, this principle creates a transition from a local, unstable process' movement to a local, stable process — the former associated with the current influx of information that precedes cooperation and the latter continuing after the cooperation with incoming information and its accumulation. This transition enables producing the cooperative phenomena, in particular, the contributions from different superimposing processes, measured by the MC. The IMD optimal consolidation process forms the information hierarchical network (IN) consisting of the model eigenvalues' sequential cooperation by three. The MC of such optimal cooperative triplets' structure is measured by the IN's triplet's code as an algorithm of the minimal program. The MC covers the Kolmogorov's complexity, which measures a deterministic order over a stochastic disorder by a minimal program, as well as the statistical complexity.The MC specific consists of providing a precise complexity measure of a dynamic irreversible process, which evaluates the aforementioned forms of complexities in bits of information. The geometrical space curvature conceals information of the cooperative structures in the cells' form, whose code, in particular, measures the cooperative complexity. The process' trajectory, located in this geometrical space, acquires a sequence of the code cells.
Use of CD44 by CD4+ Th1 and Th2 lymphocytes to roll and adhere
Authors: Bonder Claudine S. , Clark Stephen R. , Norman M. Ursula , Johnson Pauline , Kubes Paul 
Published: February 2006

AbstractLocalization of circulating lymphocytes to a site of inflammation is paramount for the development and maintenance of an immune response. In vitro studies using cell lines have previously demonstrated that rolling and adhesion of lymphocytes on endothelium requires CD44 interactions with hyaluronan (HA). To date, whether CD44 has a role in mediating CD4+-polarized T-helper 1 (Th1) and Th2 lymphocyte interactions with the endothelium in vivo is yet to be determined. In this study we used intravital microscopy to demonstrate that both Th1 and Th2 lymphocytes use CD44 to roll and adhere to tumor necrosis factor-α (TNFα)–activated microvasculature. Furthermore, chimeric studies imply that CD44 expression by both the endothelium and lymphocytes is essential for these interactions to occur. HA was also necessary for T cell–endothelial cell interactions in vivo and Th1 and Th2 cells rolled on immobilized HA in vitro via CD44. In vitro, both Th1 and Th2 lymphocytes have increased expression of CD44 and greater binding of fluorescent HA than naive cells. The interactions of Th1 and Th2 cells were entirely dependent upon both P-selectin and CD44 in vivo, but did not appear to be counter ligands in vitro. Taken together, these results suggest that CD44 and HA are key to both Th1 and Th2 lymphocyte interactions with the TNFα-activated endothelium and raises the possibility of cooperativity between the P-selectin/PSGL-1 and HA/CD44 pathways for Th1 and Th2 rolling in vivo.
Eradication of minimal residual disease in hairy cell leukemia
Authors: Ravandi Farhad , Jorgensen Jeffrey L. , O'Brien Susan M. , Verstovsek Srdan , Koller Charles A. , Faderl Stefan , Giles Francis J. , Ferrajoli Alessandra , Wierda William G. , Odinga Shirley , Huang Xuelin , Thomas Deborah A. , Freireich Emil J. , Jones Dan , Keating Michael J. , Kantarjian Hagop M. 
Published: February 2006

AbstractAlthough the nucleoside analogs cladribine and pentostatin produce high response rates in patients with hairy cell leukemia (HCL), a significant number of patients eventually relapse. Several studies have demonstrated that patients with complete remission (CR) have a longer disease-free survival. Therefore, strategies to improve on the initial response to nucleoside analog therapy are likely to be beneficial, at least for a proportion of patients. We have treated 13 patients with newly diagnosed HCL (n = 11) or after failure of one prior chemotherapy (n = 2) with cladribine (5.6 mg/m2 given intravenously over 2 hours daily for 5 days) followed by 8 weekly doses of rituximab (375 mg/m2). All patients achieved a CR and minimal residual disease (MRD) assessed by consensus primer polymerase chain reaction (PCR) or flow cytometry was eradicated in 11 (92%) of 12 and in 12 (92%) of 13 of patients, respectively. There was no decline in the absolute CD4 and CD8 lymphocyte number after rituximab. We conclude that eradication of MRD in HCL is possible. Whether this leads to a reduced risk of relapse would need to be evaluated in a larger number of patients and with longer follow-up. Disease characteristics may potentially be used to identify patients that are more likely to benefit from such additional therapy.
Biclustering of gene expression data by non-smooth non-negative matrix factorization
Authors: Carmona-Saez Pedro , Pascual-Marqui Roberto D , Tirado F , Carazo Jose M , Pascual-Montano Alberto 
Published: February 2006

Abstract

Background
The extended use of microarray technologies has enabled the generation and accumulation of gene expression datasets that contain expression levels of thousands of genes across tens or hundreds of different experimental conditions. One of the major challenges in the analysis of such datasets is to discover local structures composed by sets of genes that show coherent expression patterns across subsets of experimental conditions. These patterns may provide clues about the main biological processes associated to different physiological states.

Results
In this work we present a methodology able to cluster genes and conditions highly related in sub-portions of the data. Our approach is based on a new data mining technique, Non-smooth Non-Negative Matrix Factorization (n sNMF), able to identify localized patterns in large datasets. We assessed the potential of this methodology analyzing several synthetic datasets as well as two large and heterogeneous sets of gene expression profiles. In all cases the method was able to identify localized features related to sets of genes that show consistent expression patterns across subsets of experimental conditions. The uncovered structures showed a clear biological meaning in terms of relationships among functional annotations of genes and the phenotypes or physiological states of the associated conditions.

Conclusion
The proposed approach can be a useful tool to analyze large and heterogeneous gene expression datasets. The method is able to identify complex relationships among genes and conditions that are difficult to identify by standard clustering algorithms.
Integrating protein structures and precomputed genealogies in the Magnum database: Examples with cellular retinoid binding proteins
Authors: Bradley Michael E , Benner Steven A 
Published: February 2006

Abstract

Background
When accurate models for the divergent evolution of protein sequences are integrated with complementary biological information, such as folded protein structures, analyses of the combined data often lead to new hypotheses about molecular physiology. This represents an excellent example of how bioinformatics can be used to guide experimental research. However, progress in this direction has been slowed by the lack of a publicly available resource suitable for general use.

Results
The precomputed Magnum database offers a solution to this problem for ca. 1,800 full-length protein families with at least one crystal structure. The Magnum deliverables include 1) multiple sequence alignments, 2) mapping of alignment sites to crystal structure sites, 3) phylogenetic trees, 4) inferred ancestral sequences at internal tree nodes, and 5) amino acid replacements along tree branches. Comprehensive evaluations revealed that the automated procedures used to construct Magnum produced accurate models of how proteins divergently evolve, or genealogies, and correctly integrated these with the structural data. To demonstrate Magnum's capabilities, we asked for amino acid replacements requiring three nucleotide substitutions, located at internal protein structure sites, and occurring on short phylogenetic tree branches. In the cellular retinoid binding protein family a site that potentially modulates ligand binding affinity was discovered. Recruitment of cellular retinol binding protein to function as a lens crystallin in the diurnal gecko afforded another opportunity to showcase the predictive value of a browsable database containing branch replacement patterns integrated with protein structures.

Conclusion
We integrated two areas of protein science, evolution and structure, on a large scale and created a precomputed database, known as Magnum, which is the first freely available resource of its kind. Magnum provides evolutionary and structural bioinformatics resources that are useful for identifying experimentally testable hypotheses about the molecular basis of protein behaviors and functions, as illustrated with the examples from the cellular retinoid binding proteins.