bluuebunny/crossref_metadata_2025_split huggingface dataset:
Selective depletion of alloreactive donor lymphocytes: a novel method to reduce the severity of graft-versus-host disease in older patients undergoing matched sibling donor stem cell transplantation
Authors: Solomon Scott R. , Mielke Stephan , Savani Bipin N. , Montero Aldemar , Wisch Laura , Childs Richard , Hensel Nancy , Schindler John , Ghetie Victor , Leitman Susan F. , Mai Thao , Carter Charles S. , Kurlander Roger , Read Elizabeth J. , Vitetta Ellen S. , Barrett A. John 
Published: April 2005

AbstractWe have selectively depleted host-reactive donor T cells from peripheral blood stem cell (PBSC) transplant allografts ex vivo using an anti-CD25 immunotoxin. We report a clinical trial to decrease graft-versus-host disease (GVHD) in elderly patients receiving selectively depleted PBSC transplants from HLA-identical sibling donors. Sixteen patients (median age, 65 years [range, 51-73 years]), with advanced hematologic malignancies underwent transplantation following reduced-intensity conditioning with fludarabine and either cyclophosphamide (n = 5), melphalan (n = 5), or busulfan (n = 6). Cyclosporine was used as sole GVHD prophylaxis. The allograft contained a median of 4.5 × 106 CD34 cells/kg (range, 3.4-7.3 × 106 CD34 cells/kg) and 1.0 × 108/kg (range, 0.2-1.5 × 108/kg) selectively depleted T cells. Fifteen patients achieved sustained engraftment. The helper T-lymphocyte precursor (HTLp) frequency assay demonstrated successful (mean, 5-fold) depletion of host-reactive donor T cells, with conservation of third-party response in 9 of 11 cases tested. Actuarial rates of acute GVHD were 46% ± 13% for grades II to IV and 12% ± 8% for grades III to IV. These results suggest that allodepletion of donor cells ex vivo is clinically feasible in older patients and may reduce the rate of severe acute GVHD. Further studies with selectively depleted transplants to evaluate graft-versus-leukemia (GVL) and survival are warranted.
Building a protein name dictionary from full text: a machine learning term extraction approach
Authors: Shi Lei , Campagne Fabien 
Published: April 2005

Abstract
Background
The majority of information in the biological literature resides in full text articles, instead of abstracts. Yet, abstracts remain the focus of many publicly available literature data mining tools. Most literature mining tools rely on pre-existing lexicons of biological names, often extracted from curated gene or protein databases. This is a limitation, because such databases have low coverage of the many name variants which are used to refer to biological entities in the literature.

Results
We present an approach to recognize named entities in full text. The approach collects high frequency terms in an article, and uses support vector machines (SVM) to identify biological entity names. It is also computationally efficient and robust to noise commonly found in full text material. We use the method to create a protein name dictionary from a set of 80,528 full text articles. Only 8.3% of the names in this dictionary match SwissProt description lines. We assess the quality of the dictionary by studying its protein name recognition performance in full text.

Conclusion
This dictionary term lookup method compares favourably to other published methods, supporting the significance of our direct extraction approach. The method is strong in recognizing name variants not found in SwissProt.
A method for aligning RNA secondary structures and its application to RNA motif detection
Authors: Liu Jianghui , Wang Jason TL , Hu Jun , Tian Bin 
Published: April 2005

Abstract
Background
Alignment of RNA secondary structures is important in studying functional RNA motifs. In recent years, much progress has been made in RNA motif finding and structure alignment. However, existing tools either require a large number of prealigned structures or suffer from high time complexities. This makes it difficult for the tools to process RNAs whose prealigned structures are unavailable or process very large RNA structure databases.

Results
We present here an efficient tool called RSmatch for aligning RNA secondary structures and for motif detection. Motivated by widely used algorithms for RNA folding, we decompose an RNA secondary structure into a set of atomic structure components that are further organized by a tree model to capture the structural particularities. RSmatch can find the optimal global or local alignment between two RNA secondary structures using two scoring matrices, one for single-stranded regions and the other for double-stranded regions. The time complexity of RSmatch is O(mn) where m is the size of the query structure and n that of the subject structure. When applied to searching a structure database, RSmatch can find similar RNA substructures, and is capable of conducting multiple structure alignment and iterative database search. Therefore it can be used to identify functional RNA motifs. The accuracy of RSmatch is tested by experiments using a number of known RNA structures, including simple stem-loops and complex structures containing junctions.

Conclusion
With respect to computing efficiency and accuracy, RSmatch compares favorably with other tools for RNA structure alignment and motif detection. This tool shall be useful to researchers interested in comparing RNA structures obtained from wet lab experiments or RNA folding programs, particularly when the size of the structure dataset is large.
Valine 738 and lysine 735 in the fifth transmembrane domain of rTas1r3 mediate insensitivity towards lactisole of the rat sweet taste receptor
Authors: Winnig Marcel , Bufe Bernd , Meyerhof Wolfgang 
Published: April 2005

Abstract

Background
The sweet taste inhibitor lactisole acts on the human sweet taste receptor heteromer TAS1R2-TAS1R3 but not on its rodent counterpart. Recently, it was shown that the lactisole sensitivity of the human sweet taste receptor involves the part of TAS1R3 encompassing the seven transmembrane regions but not the huge N-terminal domain. Using mutational analysis we investigated which amino acid residues distinguish lactisole insensitive rat from sensitive human T1R3 receptors.

Results
The functional analysis of specific receptor mutants in HEK293T cells revealed that the exchange of valine 738 in the fifth transmembrane domain of rTas1r3 by an alanine is sufficient to confer lactisole sensitivity to the rat sweet taste receptor. The sensitivity of this receptor mutant is ~2 fold lower than the sensitivity of the human sweet taste receptor. Additional substitution of lysine 735 by phenylalanine in rTas1r3 results in a rat sweet taste receptor that is as sensitive to lactisole as its human counterpart. The exchange of valine 738 to alanine was accompanied by a ~50% reduction in receptor efficacy. This effect was seen with all six different sweet compounds examined.

Conclusion
The lactisole insensitivity of rat sweet taste receptor is caused by only two amino acids in transmembrane region five, which is critical for the interaction of lactisole with the sweet taste receptor. The observation that the mutant receptor simultaneously displays a generally reduced sensitivity towards all agonists suggests that the lactisole insensitivity of the rodent receptor might be more likely caused by the inaccessibility of the lactisole binding site rather then by its direct disruption.
Diseased muscles that lack dystrophin or laminin-α2 have altered compositions and proliferation of mononuclear cell populations
Authors: Girgenrath Mahasweta , Kostek Christine A , Miller Jeffrey Boone 
Published: April 2005

Abstract
Background
Multiple types of mononucleate cells reside among the multinucleate myofibers in skeletal muscles and these mononucleate cells function in muscle maintenance and repair. How neuromuscular disease might affect different types of muscle mononucleate cells had not been determined. In this study, therefore, we examined how two neuromuscular diseases, dystrophin-deficiency and laminin-α2-deficiency, altered the proliferation and composition of different subsets of muscle-derived mononucleate cells.

Methods
We used fluorescence-activated cell sorting combined with bromodeoxyuridine labeling to examine proliferation rates and compositions of mononuclear cells in diseased and healthy mouse skeletal muscle. We prepared mononucleate cells from muscles of mdx (dystrophin-deficient) or Lama2-/- (laminin-α2-deficient) mice and compared them to cells from healthy control muscles. We enumerated subsets of resident muscle cells based on Sca-1 and CD45 expression patterns and determined the proliferation of each cell subset in vivo by BrdU incorporation.

Results
We found that the proliferation and composition of the mononucleate cells in dystrophin-deficient and laminin-α2-deficient diseased muscles are different than in healthy muscle. The mdx and Lama2-/- muscles showed similar significant increases in CD45+ cells compared to healthy muscle. Changes in proliferation, however, differed between the two diseases with proliferation increased in mdx and decreased in Lama2-/- muscles compared to healthy muscles. In particular, the most abundant Sca-1-/CD45- subset, which contains muscle precursor cells, had increased proliferation in mdx muscle but decreased proliferation in Lama2-/- muscles.

Conclusion
The similar increases in CD45+ cells, but opposite changes in proliferation of muscle precursor cells, may underlie aspects of the distinct pathologies in the two diseases.
Add-on topiramate reduces weight in overweight patients with affective disorders: a clinical case series
Authors: Kirov George , Tredget John 
Published: April 2005

Abstract
Background
The weight-gain caused by many psychotropic drugs is a major cause for poor compliance with such medications and could also increase cardio-vascular morbidity among psychiatric patients. Recent reports have shown that the anticonvulsant topiramate causes weight loss in various patient groups. The drug has also shown effectiveness in open trials as a mood stabilizer in patients with affective disorders, but not in controlled trials in the acute treatment of mania. We used topiramate to treat 12 patients with affective disorders who had a body-mass index >30 kg/m2.

Methods
Topiramate was prescribed as part of our routine clinical practice, as an add-on medication, or as a replacement of a mood stabilizer. Patients' weight was recorded in 1 to 2 monthly intervals. Patients were followed up for between 6 and 12 months. The final dose of topiramate varied from 200 to 600 mg/day.

Results
Topiramate was effective in reducing the weight in 10 out of the 12 patients. At six months the 12 patients had lost a mean of 7.75 kg (SD = 6.9 kg, p < 0.001) and at 12 months 9 patients had lost a mean of 9.61 kg (SD = 6.7 kg, p = 0.003). Three patients stopped the treatment: one due to side effects, one due to possible side effects, and one suffered a manic relapse and showed no sustained weight loss. There were no other clear changes in the course of illness of the patients.

Conclusion
The evidence of a strong weight-reducing potential of topiramate is indisputable and clinically significant. Topiramate could be considered in the treatment of bipolar patients who are overweight, or whose concerns about weight gain compromise their compliance with long-term prophylactic medication. So far there is no evidence that topiramate has anti-manic effect and it should not be used as monotherapy.
Enhanced levels of Hsulf-1 interfere with heparin-binding growth factor signaling in pancreatic cancer
Authors: Li Junsheng , Kleeff Jörg , Abiatari Ivane , Kayed Hany , Giese Nathalia A , Felix Klaus , Giese Thomas , Büchler Markus W , Friess Helmut 
Published: April 2005

Abstract
Hsulf-1 is a newly identified enzyme, which has the ability to decrease the growth of hepatocellular, ovarian, and head and neck squamous cell carcinoma cells by interfering with heparin-binding growth factor signaling. Since pancreatic cancers over-express a number of heparin-binding growth factors and their receptors, the expression and function of this enzyme in pancreatic cancer was analyzed.

Results

Pancreatic cancer samples expressed significantly (22.5-fold) increased Hsulf-1 mRNA levels compared to normal controls, and Hsulf-1 mRNA was localized in the cancer cells themselves as well as in peritumoral fibroblasts. 4 out of 8 examined pancreatic cancer cell lines expressed Hsulf-1, whereas its expression was below the level of detection in the other cell lines. Stable transfection of the Hsulf-1 negative Panc-1 pancreatic cancer cell line with a full length Hsulf-1 expression vector resulted in increased sulfatase activity and decreased cell-surface heparan-sulfate proteoglycan (HSPG) sulfation. Hsulf-1 expression reduced both anchorage-dependent and -independent cell growth and decreased FGF-2 mediated cell growth and invasion in this cell line.

Conclusion

High expression of Hsulf-1 occurs in the stromal elements as well as in the tumor cells in pancreatic cancer and interferes with heparin-binding growth factor signaling.
Combination of qualitative and quantitative methods for developing a new Health Related Quality of Life measure for patients with anogenital warts
Authors: Badia Xavier , Colombo Jose Antonio , Lara Nuria , Llorens M Angels , Olmos Luis , de los Terreros Miguel Sainz , Varela Jose Antonio , Vilata Juan Jose 
Published: April 2005

Abstract

Background
Anogenital warts are the most easily recognized sign of genital Human Papilloma Virus infection. The objective was to develop a short, valid and reliable questionnaire to measure Health Related Quality of Life (HRQL) in patients with anogenital warts.

Methods
First a literature review was performed to identify relevant papers describing the impact of anogenital warts in HRQL; second the main domains were identified by some experts in a focus group, and third in-depth-semi-structured interviews were conducted in patients with anogenital warts to identify the initial set of items. A qualitative reduction of the initial set of items was performed based on the mean scoring of the experts for the three scales: clarity, frequency and importance. The initial questionnaire was pilot tested in 135 patients. Rasch analysis was performed with the results of the questionnaire in order to refine the instrument. Spearman's correlation was calculated between the initial questionnaire and the reduced version. Additionally the measurement properties (validity and reliability) of the resulting final questionnaire were tested and compared using standard procedures (Cronbach's Alpha and item-total correlation).

Results
the main domains identified as affected in patient's life were: sexual, colleagues and partner relationships. After a proper qualitative reduction the initial set of 134 items was reduced to 22. The questionnaire was pilot tested in 135 patients and two dimensions were identified after the multifactorial analysis: emotional dimension and sexual activity dimension. As a result of the Rasch analysis the questionnaire was reduced to 10 items. High correlation was found between the initial and the reduced version for the two dimensions. Cronbach's alpha values were acceptable (0.86).

Conclusion
The initial 22 items questionnaire was reduced by Rasch analysis to a version of 10 items, with two dimensions: emotional and sexual. The results suggest the adequacy of the 10 items to evaluate HRQL of patients with anogenital warts in a valid and reliable way.
Acute phase reactants add little to composite disease activity indices for rheumatoid arthritis: validation of a clinical activity score
Authors: Aletaha Daniel , Nell Valerie PK , Stamm Tanja , Uffmann Martin , Pflugbeil Stephan , Machold Klaus , Smolen Josef S 
Published: April 2005

Abstract
Introduction
Frequent assessments of rheumatoid arthritis (RA) disease activity allow timely adaptation of therapy, which is essential in preventing disease progression. However, values of acute phase reactants (APRs) are needed to calculate current composite activity indices, such as the Disease Activity Score (DAS)28, the DAS28-CRP (i.e. the DAS28 using C-reactive protein instead of erythrocyte sedimentation rate) and the Simplified Disease Activity Index (SDAI). We hypothesized that APRs make limited contribution to the SDAI, and that an SDAI-modification eliminating APRs – termed the Clinical Disease Activity Index (CDAI; i.e. the sum of tender and swollen joint counts [28 joints] and patient and physician global assessments [in cm]) – would have comparable validity in clinical cohorts.

Method
Data sources comprised an observational cohort of 767 RA patients (average disease duration 8.1 ± 10.6 years), and an independent inception cohort of 106 patients (disease duration 11.5 ± 12.5 weeks) who were followed prospectively.

Results
Our clinically based hypothesis was statistically supported: APRs accounted only for 15% of the DAS28, and for 5% of the SDAI and the DAS28-CRP. In both cohorts the CDAI correlated strongly with DAS28 (R = 0.89–0.90) and comparably to the correlation of SDAI with DAS28 (R = 0.90–0.91). In additional analyses, the CDAI when compared to the SDAI and the DAS28 agreed with a weighted kappa of 0.70 and 0.79, respectively, and comparably to the agreement between DAS28 and DAS28-CRP. All three scores correlated similarly with Health Assessment Questionnaire (HAQ) scores (R = 0.45–0.47). The average changes in all scores were greater in patients with better American College of Rheumatology response (P < 0.0001, analysis of variance; discriminant validity). All scores exhibited similar correlations with radiological progression (construct validity) over 3 years (R = 0.54–0.58; P < 0.0001).

Conclusion
APRs add little information on top (and independent) of the combination of clinical variables included in the SDAI. A purely clinical score is a valid measure of disease activity and will have its greatest merits in clinical practice rather than research, where APRs are usually always available. The CDAI may facilitate immediate and consistent treatment decisions and help to improve patient outcomes in the longer term.
Augmented IL-10 production and redox-dependent signaling pathways in glucose-6-phosphate dehydrogenase-deficient mouse peritoneal macrophages
Authors: Wilmanski Jeanette , Siddiqi Muhammad , Deitch Edwin A , Spolarics Zoltán 
Published: April 2005

AbstractGlucose-6-phosphate dehydrogenase (G6PD) supports cellular antioxidant pathways. G6PD deficiency is associated with malaria protection but was shown to worsen the clinical course to injury. This study tested whether G6PD deficiency manifests in altered cytokine responses using peritoneal macrophages from a G6PD-deficient mouse model with a degree of defect similar to the common type A– human G6PD deficiency. Lipopolysaccharide (LPS)-induced interleukin (IL)-10 and IL-12 production was doubled in G6PD-deficient macrophages compared with wild-type (WT). Protein kinase C (PKC) activation by phorbol-ester prior to LPS resulted in a fivefold greater IL-10 production in G6PD-deficient macrophages compared with WT. Interferon-γ treatment prior to LPS augmented IL-12 production in G6PD-deficient and WT macrophages and partially inhibited IL-10 production by G6PD-deficient macrophages. The antioxidants (N-acetyl-L-cysteine and glutathione ethyl-ester) blunted IL-10 and IL-12 production, indicating a role for oxidative stress in the observed response differences between deficient and WT macrophages. LPS-induced activation of nuclear factor-κB, cyclic adenosine monophosphate response element-binding protein, and specificity protein 3 was augmented in G6PD-deficient cells compared with WT. The PKCδ inhibitor Rottlerin inhibited IL-10 and IL-12 production at different 50% effective-dose concentrations between deficient and WT macrophages, indicating elevated PKCδ activity in deficient cells. This study reveals that activated G6PD-deficient macrophages display an augmented production of cytokines with a prominent impact on IL-10 production. The altered cytokine responses are associated with augmented activation of redox-dependent transcription factors and PKCδ. Alterations in signaling pathways and associated changes in cytokine production may play a role in modulating the inflammatory responses following bacterial or malarial infections in G6PD deficiency.
Leukocyte apoptosis and its significance in sepsis and shock
Authors: Wesche Doreen E , Lomas-Neira Joanne L , Perl Mario , Chung Chun-Shiang , Ayala Alfred 
Published: April 2005

AbstractSepsis and multiple organ failure continue to be significant problems among trauma, burn, and the critically ill patient population. Thus, a number of laboratories have focused on understanding the role of altered apoptotic cell death in contributing to immune and organ dysfunction seen in sepsis and shock. Immune cells that undergo altered apoptotic changes include neutrophils, macrophages, dendritic cells, as well as various lymphocyte populations. Evidence of epithelial as well as endothelial cell apoptotic changes has also been reported. Although mediators such as steroids, tumor necrosis factor, nitric oxide, C5a, and Fas ligand (FasL) appear to contribute to the apoptotic changes, their effects are tissue- and cell population-selective. As inhibiting Fas-FasL signaling (e.g., gene deficiency, Fas fusion protein, or Fas short interfering RNA administration), caspase inhibition (caspase mimetic peptides), and/or the overexpression of downstream antiapoptotic molecules (e.g., Bcl-2, Akt) improve survival of septic mice, it not only demonstrates the pathological significance of this process but points to novel targets for the treatment of sepsis.
T cells from paroxysmal nocturnal haemoglobinuria (PNH) patients show an altered CD40-dependent pathway
Authors: Terrazzano Giuseppe , Sica Michela , Becchimanzi Cristina , Costantini Silvia , Rotoli Bruno , Zappacosta Serafino , Alfinito Fiorella , Ruggiero Giuseppina 
Published: April 2005

AbstractParoxysmal nocturnal haemoglobinuria (PNH) is a haematopoiesis disorder characterized by the expansion of a stem cell bearing a somatic mutation in the phosphatidylinositol glycan-A (PIG-A) gene, which is involved in the biosynthesis of the glycosylphosphatidylinositol (GPI) anchor. A number of data suggest the inability of the PIG-A mutation to account alone for the clonal dominance of the GPI-defective clone and for the development of PNH. In this context, additional immune-mediated mechanisms have been hypothesized. We focused on the analysis of T lymphocytes in three PNH patients bearing a mixed GPI+ and GPI– T cell population and showing a marked cytopenia. To analyze the biological mechanisms underlying the control of T cell homeostasis in PNH, we addressed the study of CD40-dependent pathways, suggested to be of crucial relevance for the control of autoreactive T cell clones. Our data revealed significant, functional alterations in GPI+ and GPI– T cell compartments. In the GPI– T cells, severe defects in T cell receptor-dependent proliferation, interferon-γ production, CD25, CD54, and human leukocyte antigen-DR surface expression were observed. By contrast, GPI+ T lymphocytes showed a significant increase of all these parameters, and the analysis of CD40-dependent pathways revealed a functional persistence of CD154 expression on the CD48+CD4+ lymphocytes. The alterations of the GPI+ T cell subset could be involved in the biological mechanisms underlying PNH pathogenesis.