bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mutations in the ATM gene lead to impaired overall and treatment-free survival that is independent of IGVH mutation status in patients with B-CLL
Authors: Austen Belinda , Powell Judith E. , Alvi Azra , Edwards Ian , Hooper Laura , Starczynski Jane , Taylor A. Malcolm R. , Fegan Christopher , Moss Paul , Stankovic Tatjana 
Published: July 2005

AbstractThe ataxia telangiectasia mutated (ATM) protein is the principal activator of the p53 protein in the response to DNA double-strand breaks. Mutations in the ATM gene have been previously found in B-cell chronic lymphocytic leukemias (B-CLLs) but their clinical significance is unknown. We analyzed 155 CLL tumors and found 12% with ATM mutations and 4% with TP53 mutations; 2 tumors contained mutations in both genes. Retrospective analysis on selected samples indicated that the ATM mutations were usually present at diagnosis. Compared with patients with wild-type ATM/TP53 genes, patients with ATM mutations had statistically significantly reduced overall and treatment-free survival. Although present in both IGVH mutation subgroups, ATM mutations were associated with unmutated IGVH genes and they provided independent prognostic information on multivariate analysis. Mutations in the ATM gene resulted in impaired in vitro DNA damage responses. Tumors with ATM mutations only partially correlated with tumors with loss of an ATM allele through an 11q deletion and, interestingly, those 11q-deleted tumors with a second wild-type ATM allele had a preserved DNA damage response. The majority of patients with ATM mutations were refractory to DNA damaging chemotherapeutic drugs and as such might benefit from therapies that bypass the ATM/p53 pathway.
Loss of EBNA1-specific memory CD4+ and CD8+ T cells in HIV-infected patients progressing to AIDS-related non-Hodgkin lymphoma
Authors: Piriou Erwan , van Dort Karel , Nanlohy Nening M. , van Oers Marinus H. J. , Miedema Frank , van Baarle Debbie 
Published: July 2005

AbstractWe previously observed a loss of Epstein-Barr virus (EBV)–specific CD8+ T cells in subjects progressing to EBV-related non-Hodgkin lymphoma (NHL), correlating with loss of CD4+ T cells. The aim of the present study was to determine the role of EBV-specific CD4+ T cells in the development of NHL during chronic HIV infection. To this end, CD4+ and CD8+ memory T cells, capable of both proliferation and subsequent interferon γ (IFNγ) production, directed against a latent (Epstein-Barr virus nuclear antigen 1 [EBNA1]) and a lytic (BamH fragment Z left frame 1 [BZLF1]) EBV antigen were studied longitudinally in 9 progressors to NHL, 4 progressors to non–EBV-related AIDS, and 4 slow progressors to AIDS. In all 3 groups we observed a decline of EBV-specific memory CD4+ and CD8+ T-cell responses during HIV infection. However, whereas latent antigen EBNA1-specific CD4+ T cells were lost well before diagnosis in all subjects who developed an AIDS-related NHL (and EBNA1-specific CD8+ T cells were significantly lower compared with the other groups), these cells were better preserved in progressors to non–EBV-related disease and slow progressors. Loss of EBNA1-specific T-cell immunity thus might be important for progression to NHL. Interestingly, BZLF1-specific T cells were not lost in all progressors to NHL, suggesting a different function of these cells in the surveillance of EBV-infected B cells.
Transduction of CLL cells by CD40 ligand enhances an antigen-specific immune recognition by autologous T cells
Authors: Mayr Christine , Kofler David M. , Büning Hildegard , Bund Dagmar , Hallek Michael , Wendtner Clemens-Martin 
Published: July 2005

AbstractSeveral features of chronic lymphocytic leukemia (CLL) suggest that immune-based strategies may have therapeutic potential. A promising approach is provided by the transduction of CLL cells with CD40 ligand (CD40L) by viral vectors to enhance their immunogenicity. We compared the antigen-presenting capacity of CD40L-transduced CLL cells with mock-transduced or CD40L-stimulated CLL cells (CD40-CLL). A significantly higher number of T cells could be expanded using CD40L-transduced CLL cells as antigen-presenting cells (APCs) compared with the control group (P = .008). Using 5 different CLL-associated tumor antigens, including fibromodulin, MDM2 (murine double minute 2), survivin, p53, and KW-13, we show in interferon-γ (IFN-γ) enzyme-linked immunospot (ELISPOT) assays after 35 days of in vitro culture that the number of antigen-specific autologous T cells was also significantly higher when CD40L-transduced CLL cells were used as APCs (P &lt; .001). Thus, CD40L-transduced CLL cells are able to induce an antigen-specific T-cell response and might be superior to CD40-CLL cells for immune-based therapeutic strategies in CLL.
SeqX: a tool to detect, analyze and visualize residue co-locations in protein and nucleic acid structures
Authors: Biro Jan C , Fördös Gergely 
Published: July 2005

Abstract
Background
The interacting residues of protein and nucleic acid sequences are close to each other – they are co-located. Structure databases (like Protein Data Bank, PDB and Nucleic Acid Data Bank, NDB) contain all information about these co-locations; however it is not an easy task to penetrate this complex information. We developed a JAVA tool, called SeqX for this purpose.

Results
SeqX tool is useful to detect, analyze and visualize residue co-locations in protein and nucleic acid structures. The user
a. selects a structure from PDB;
b. chooses an atom that is commonly present in every residues of the nucleic acid and/or protein structure(s)
c. defines a distance from these atoms (3–15 Å). The SeqX tool detects every residue that is located within the defined distances from the defined "backbone" atom(s); provides a DotPlot-like visualization (Residues Contact Map), and calculates the frequency of every possible residue pairs (Residue Contact Table) in the observed structure. It is possible to exclude +/- 1 to 10 neighbor residues in the same polymeric chain from detection, which greatly improves the specificity of detections (up to 60% when tested on dsDNA). Results obtained on protein structures showed highly significant correlations with results obtained from literature (p < 0.0001, n = 210, four different subsets). The co-location frequency of physico-chemically compatible amino acids is significantly higher than is calculated and expected in random protein sequences (p < 0.0001, n = 80).

Conclusion
The tool is simple and easy to use and provides a quick and reliable visualization and analyses of residue co-locations in protein and nucleic acid structures.

Availability and requirements
http://janbiro.com/Downloads.html SeqX, Java J2SE Runtime Environment 5.0 (available from [see Additional file 1] http://www.sun.com) and at least a 1 GHz processor and with a minimum 256 Mb RAM. Source codes are available from the authors.
Systematic determination of the mosaic structure of bacterial genomes: species backbone versus strain-specific loops
Authors: Chiapello H , Bourgait I , Sourivong F , Heuclin G , Gendrault-Jacquemard A , Petit M-A , El Karoui M 
Published: July 2005

Abstract
Background
Public databases now contain multitude of complete bacterial genomes, including several genomes of the same species. The available data offers new opportunities to address questions about bacterial genome evolution, a task that requires reliable fine comparison data of closely related genomes. Recent analyses have shown, using pairwise whole genome alignments, that it is possible to segment bacterial genomes into a common conserved backbone and strain-specific sequences called loops.

Results
Here, we generalize this approach and propose a strategy that allows systematic and non-biased genome segmentation based on multiple genome alignments. Segmentation analyses, as applied to 13 different bacterial species, confirmed the feasibility of our approach to discern the 'mosaic' organization of bacterial genomes. Segmentation results are available through a Web interface permitting functional analysis, extraction and visualization of the backbone/loops structure of documented genomes. To illustrate the potential of this approach, we performed a precise analysis of the mosaic organization of three E. coli strains and functional characterization of the loops.

Conclusion
The segmentation results including the backbone/loops structure of 13 bacterial species genomes are new and available for use by the scientific community at the URL: http://genome.jouy.inra.fr/mosaic.
Protein subcellular localization prediction for Gram-negative bacteria using amino acid subalphabets and a combination of multiple support vector machines
Authors: Wang Jiren , Sung Wing-Kin , Krishnan Arun , Li Kuo-Bin 
Published: July 2005

AbstractBackgroundPredicting the subcellular localization of proteins is important for determining the function of proteins. Previous works focused on predicting protein localization in Gram-negative bacteria obtained good results. However, these methods had relatively low accuracies for the localization of extracellular proteins. This paper studies ways to improve the accuracy for predicting extracellular localization in Gram-negative bacteria.ResultsWe have developed a system for predicting the subcellular localization of proteins for Gram-negative bacteria based on amino acid subalphabets and a combination of multiple support vector machines. The recall of the extracellular site and overall recall of our predictor reach 86.0% and 89.8%, respectively, in 5-fold cross-validation. To the best of our knowledge, these are the most accurate results for predicting subcellular localization in Gram-negative bacteria.ConclusionClustering 20 amino acids into a few groups by the proposed greedy algorithm provides a new way to extract features from protein sequences to cover more adjacent amino acids and hence reduce the dimensionality of the input vector of protein features. It was observed that a good amino acid grouping leads to an increase in prediction performance. Furthermore, a proper choice of a subset of complementary support vector machines constructed by different features of proteins maximizes the prediction accuracy.
Muscle regeneration in dystrophin-deficient mdx mice studied by gene expression profiling
Authors: Turk R , Sterrenburg E , de Meijer EJ , van Ommen G-JB , den Dunnen JT , 't Hoen PAC 
Published: July 2005

Abstract

Background
Duchenne muscular dystrophy (DMD), caused by mutations in the dystrophin gene, is lethal. In contrast, dystrophin-deficient mdx mice recover due to effective regeneration of affected muscle tissue. To characterize the molecular processes associated with regeneration, we compared gene expression levels in hindlimb muscle tissue of mdx and control mice at 9 timepoints, ranging from 1–20 weeks of age.

Results
Out of 7776 genes, 1735 were differentially expressed between mdx and control muscle at at least one timepoint (p < 0.05 after Bonferroni correction). We found that genes coding for components of the dystrophin-associated glycoprotein complex are generally downregulated in the mdx mouse. Based on functional characteristics such as membrane localization, signal transduction, and transcriptional activation, 166 differentially expressed genes with possible functions in regeneration were analyzed in more detail. The majority of these genes peak at the age of 8 weeks, where the regeneration activity is maximal. The following pathways are activated, as shown by upregulation of multiple members per signalling pathway: the Notch-Delta pathway that plays a role in the activation of satellite cells, and the Bmp15 and Neuregulin 3 signalling pathways that may regulate proliferation and differentiation of satellite cells. In DMD patients, only few of the identified regeneration-associated genes were found activated, indicating less efficient regeneration processes in humans.

Conclusion
Based on the observed expression profiles, we describe a model for muscle regeneration in mdx mice, which may provide new leads for development of DMD therapies based on the improvement of muscle regeneration efficacy.
Estren promotes androgen phenotypes in primary lymphoid organs and submandibular glands
Authors: Islander Ulrika , Hasséus Bengt , Erlandsson Malin C , Jochems Caroline , Skrtic Sofia Movérare , Lindberg Marie , Gustafsson Jan-Åke , Ohlsson Claes , Carlsten Hans 
Published: July 2005

Abstract

Background
Estrogens and androgens have extensive effects on the immune system, for example they suppress both T and B lymphopoiesis in thymus and bone marrow. Submandibular glands are sexually dimorphic in rodents, resulting in larger granular convoluted tubules in males compared to females. The aim of the present experiments was to investigate the estrogenic and androgenic effects of 4-estren-3α,17β-diol (estren) on thymus, bone marrow and submandibular glands, and compare the effects to those of 17β-estradiol (E2) and 5α-dihydrotestosterone (DHT), respectively. Estrogen receptors (ERs) were blocked by treatment of mice with the ER-antagonist ICI 182,780; also, knock-out mice lacking one or both ERs were used.

Results
As expected, the presence of functional ERs was mandatory for all the effects of E2. Similar to DHT-treatment, estren-treatment resulted in decreased thymus weight, as well as decreased frequency of bone marrow B cells. Treatment with estren or DHT also resulted in a shift in submandibular glands towards an androgen phenotype. All the effects of estren and DHT were independent of ERs.

Conclusion
Our study is the first to show that estren has similar effects as the androgen DHT on lymphopoiesis in thymus and bone marrow, and on submandibular glands, and that these effects are independent of estrogen receptors. This supports the hypothesis of estren being able to signal through the androgen receptor.
Pharmacy-based needle exchange in New Zealand: a review of services
Authors: Sheridan Janie , Henderson Charles , Greenhill Nicola , Smith Andrew 
Published: July 2005

Background
New Zealand has been offering needle exchange services since 1987. Over 170 community pharmacies are involved in the provision of this service. However, no recent detailed review of New Zealand's pharmacy-based needle exchange has been published. This study aimed to explore service provision, identify problems faced by pharmacists, and look for improvements to services.

Methods

The study used a cross-sectional survey of all needle exchange pharmacies. Postal questionnaires were used with postal and telephone follow-up.

Results

A response rate of 88% was obtained overall. Pharmacists had been providing the service for a mean of 6 years. Pharmacies had given out an average of 130 injecting units, in a mean of 62 transactions to a mean of 17 clients in the 4 weeks prior to completing the questionnaire. The majority had not incurred problems such as violence or intoxicated clients in the last 12 months, although almost one third had experienced shoplifting which they associated with service provision. Training and improving return rates were identified as potential areas for further development.

Conclusion

New Zealand needle exchange pharmacies are providing services to a number of clients. The majority of service providers had been involved for a number of years, indicating the problems incurred had not caused them to withdraw their services – findings which echo those from the UK. Further training and support, including an exploration of improving return rates may be needed in the future.
Ku protein as a potential human T-cell leukemia virus type 1 (HTLV-1) Tax target in clastogenic chromosomal instability of mammalian cells
Authors: Majone Franca , Luisetto Roberto , Zamboni Daniela , Iwanaga Yoichi , Jeang Kuan-Teh 
Published: July 2005

Abstract
The HTLV-1 Tax oncoprotein rapidly induces cytogenetic damage which can be measured by a significant increase in the number of micronuclei (MN) in cells. Tax is thought to have both aneuploidogenic and clastogenic effects. To examine the cellular target for Tax which might mechanistically explain the clastogenic phenomenon, we tested the ability of Tax to induce MN in rodents cells genetically defective for either the Ku80 protein or the catalytic subunit of DNA protein kinase (DNAPKcs). We found that cells genetically mutated in Ku80 were refractory to Tax's induction of MN while cells knocked-out for DNAPKcs showed increased number of Tax-induced MN. Using a cytogenetic method termed FISHI (Fluorescent In Situ Hybridization and Incorporation) which measures the number of DNA-breaks in cells that contained unprotected 3'-OH ends, we observed that Tax increased the prevalence of unprotected DNA breaks in Ku80-intact cells, but not in Ku80-mutated cells. Taken together, our findings suggest Ku80 as a cellular factor targeted by Tax in engendering clastogenic DNA damage.
Antineutrophil cytoplasmic antibody (ANCA)-associated autoimmune diseases induced by antithyroid drugs: comparison with idiopathic ANCA vasculitides
Authors: Bonaci-Nikolic Branka , Nikolic Milos M , Andrejevic Sladjana , Zoric Svetlana , Bukilica Mirjana 
Published: July 2005

AbstractClinical and serological profiles of idiopathic and drug-induced autoimmune diseases can be very similar. We compared data from idiopathic and antithyroid drug (ATD)-induced antineutrophil cytoplasmic antibody (ANCA)-positive patients. From 1993 to 2003, 2474 patients were tested for ANCA in the Laboratory for Allergy and Clinical Immunology in Belgrade. Out of 2474 patients, 72 (2.9%) were anti-proteinase 3 (PR3)- or anti-myeloperoxidase (MPO)-positive and their clinical and serological data were analyzed. The first group consisted of ANCA-associated idiopathic systemic vasculitis (ISV) diagnosed in 56/72 patients: 29 Wegener's granulomatosis (WG), 23 microscopic polyangiitis (MPA) and four Churg-Strauss syndrome. The second group consisted of 16/72 patients who became ANCA-positive during ATD therapy (12 receiving propylthiouracil and four receiving methimazole). We determined ANCA and antinuclear (ANA) antibodies by indirect immunofluorescence; PR3-ANCA, MPO-ANCA, anticardiolipin (aCL) and antihistone antibodies (AHA) by ELISA; and cryoglobulins by precipitation. Complement components C3 and C4, alpha-1 antitrypsin (α1 AT) and C reactive protein (CR-P) were measured by nephelometry. Renal lesions were present in 3/16 (18.8%) ATD-treated patients and in 42/56 (75%) ISV patients (p <0.001). Skin lesions occurred in 10/16 (62.5%) ATD-treated patients and 14/56 (25%) ISV patients (p <0.01). ATD-treated patients more frequently had MPO-ANCA, ANA, AHA, aCL, cryoglobulins and low C4 (p <0.01). ISV patients more frequently had low α1 AT (p = 0.059) and high CR-P (p <0.001). Of 16 ATD-treated patients, four had drug-induced ANCA vasculitis (three MPA and one WG), while 12 had lupus-like disease (LLD). Of 56 ISV patients, 13 died and eight developed terminal renal failure (TRF). There was no lethality in the ATD-treated group, but 1/16 with methimazole-induced MPA developed pulmonary-renal syndrome with progression to TRF. ANCA-positive ISV had a more severe course in comparison with ATD-induced ANCA-positive diseases. Clinically and serologically ANCA-positive ATD-treated patients can be divided into two groups: the first consisting of patients with drug-induced WG or MPA which resemble ISV and the second consisting of patients with LLD. Different serological profiles could help in the differential diagnosis and adequate therapeutic approach to ANCA-positive ATD-treated patients with symptoms of systemic disease.
Anatomic Analysis of the Transforaminal Ligament in the Lumbar Intervertebral Foramen
Authors: Min Jun-Hong , Kang Shin-Hyuk , Lee Jang-Bo , Cho Tai-Hyoung , Suh Jung-Guen 
Published: July 2005

Abstract

OBJECTIVE:
The objective of this study was to evaluate the clinical significance of the transforaminal ligaments (TFLs) in relation to the area of the lumbar intervertebral foramen (IVF) by analyzing cadaveric spines.

METHODS:
One hundred ninety-eight cadaveric lumbar IVFs were studied, and the existence and type of TFLs were identified. All IVFs were photographed, and the images were saved. The areas of the IVFs and TFLs were measured with the Scion Image for Windows image analysis program.

RESULTS:
TFLs were found in 82.8% of the IVFs. The oblique inferior transforaminal ligament was the most common. The mean area of the IVFs was 155.8 ± 51.1 mm2, and the mean area occupied by the TFLs was 46.3 ± 37.6 mm2. The mean percentage of the IVF area occupied by the TFLs was 28.5 ± 18.8%.

CONCLUSION:
TFLs are common structures in the IVF and may reduce the space available for the spinal nerve root within the IVF. In this circumstance, any compromise of the IVF may impinge on the nerve root.
Automated Three-dimensional Volume Rendering of Helical Computed Tomographic Angiography for Aneurysms: An Advanced Application of Neuronavigation Technology
Authors: Benvenuti Lucia , Chibbaro Salvatore , Carnesecchi Stefano , Pulerà Flavio , Gagliardi Rolando 
Published: July 2005

Abstract

OBJECTIVE:
To introduce the possibility of volume-rendered helical computed tomographic (CT) angiographic data sets by use of Medtronic StealthStation Treon surgical navigation technology (Medtronic Surgical Navigation Technologies, Louisville, CO) and to evaluate the clinical usefulness of the method in planning and performing surgical treatment of intracranial aneurysms.

METHODS:
Between November 2002 and July 2003, we studied 15 patients with suspected intracranial aneurysms. All patients but two received conventional digital subtraction angiography, which failed to provide the requested information. Helical CT angiography was performed in all patients, and data sets were transferred to the StealthStation system across an electronic network to be automatically postprocessed by use of three-dimensional (3-D) volume rendering. The 3-D volume-rendered images were accurately analyzed to obtain more complete information about the aneurysm and to provide accurate treatment planning. In all patients, the 3-D volume-rendered model was displayed on the screen of the StealthStation system for the duration of the surgical procedure and compared with the intraoperative image.

RESULTS:
Data sets from CT angiography were automatically postprocessed by the StealthStation in seconds with excellent results, providing us, before and during surgery, with additional information not always available on traditional digital subtraction angiographic investigation. Because of the very short time necessary to complete this process (&lt;5 min to obtain 3-D volume-rendered images), it was possible to perform emergency clipping of the aneurysms in two patients who had been admitted in very compromised neurological conditions. In 12 patients, integrated digital subtraction angiography and automated 3-D volume-rendered images allowed an accurate presurgical evaluation. Furthermore, in all patients on whom surgery was performed, aneurysms were found in the exact location and with the same anatomic features as depicted by the 3-D volume-rendered models.

CONCLUSION:
Reports in the literature indicate that information gathered by CT angiography with volume rendering shows a significant impact on aneurysm management. The StealthStation system upgraded with the adequate algorithm seems to provide a time- and cost-effective method of performing automated 3-D volume rendering of CT angiography and provides an interesting alternative to the available investigation modalities in case of emergency.