bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cutting Edge: Limiting MHC Class II Expression to Dendritic Cells Alters the Ability to Develop Th2- Dependent Allergic Airway Inflammation
Authors: Niu Naiqian , Laufer Terri , Homer Robert J. , Cohn Lauren 
Published: July 2009

Abstract
In allergic airway inflammation, dendritic cells (DCs) are required for Th2 generation, recruitment, and activation in the respiratory tract. DCs have been shown to be necessary and sufficient for the induction of Th1 immune responses. In Th2 immunity and allergic airway inflammation, the ability of a DC to function as the sole APC has not been tested. We show that CD11c/Aβb mice with MHC class II expression restricted to CD11c-expressing DCs develop airway neutrophilia rather than allergic airway inflammation. Although CD11c/Aβb mice are capable of Th2 recruitment and activation in the lung, Th2 priming in CD11c/Aβb mice results in IFN-γ production. Effective Th2 generation and allergic airway inflammation was achieved in CD11c/Aβb mice after treatment with anti-IFN-γ. These studies show that DCs alone cannot drive the development of Th2 cells but require an additional MHC class II signal to stimulate effective Th2 immunity.
The graphemic/motor frontal area Exner's area revisited
Authors: Roux Franck‐Emmanuel , Dufor Olivier , Giussani Carlo , Wamain Yannick , Draper Louisa , Longcamp Marieke , Démonet Jean‐François 
Published: July 2009

AbstractObjectiveIn 1881, Exner first described a “graphic motor image center” in the middle frontal gyrus. Current psycholinguistic models of handwriting involve the conversion of abstract, orthographic representations into motor representations before a sequence of appropriate hand movements is produced. Direct cortical stimulation and functional magnetic resonance imaging (fMRI) were used to study the human frontal areas involved in writing.MethodsCortical electrical stimulation mapping was used intraoperatively in 12 patients during the removal of brain tumors to identify the areas involved in oral language (sentence reading and naming) and writing, and to spare them during surgery. The fMRI activation experiment involved 12 right‐handed and 12 left‐handed healthy volunteers using word dictation (without visual control) and 2 control tasks.ResultsDirect cortical electrical stimulation of restricted areas rostral to the primary motor hand area (Brodmann area [BA] 6) impaired handwriting in 6 patients, without disturbing hand movements or oral language tasks. In 6 other patients, stimulation of lower frontal regions showed deficits combining handwriting with other language tasks. fMRI also revealed selective activation during word handwriting in left versus right BA6 depending on handedness. This area was anatomically matched to those areas that affected handwriting on electrical stimulation.InterpretationAn area in middle frontal gyrus (BA6) that we have termed the graphemic/motor frontal area supports bridging between orthography and motor programs specific to handwriting. Ann Neurol 2009;66:537–545
Back‐propagation artificial neural network and attenuated total reflectance‐Fourier transform infrared spectroscopy for diagnosis of basal cell carcinoma by blood sample analysis
Authors: Khanmohammadi Mohammadreza , Garmarudi Amir Bagheri , Ghasemi Keyvan 
Published: July 2009

AbstractA diagnostic method for the cancer, based on investigation of infrared spectra of blood samples, has been developed. The two‐layer modified principal component feed forward back‐propagation artificial neural network (BP‐ANN) was used to classify the attenuated total reflectance‐Fourier transform infrared (ATR‐FTIR) spectra of blood samples obtained from healthy people and those with basal cell carcinoma (BCC). Results showed 98.33% of accuracy, in comparison with the current clinical methods. In the first step, 20 blood samples (10 normal and 10 cancer cases) were applied to construct the calibration model. Spectroscopic studies were performed in 900–1800 cm−1 spectral region with 3.85 cm−1 data space. In order to modify the capability of ANN in prediction of test samples, two different algorithms were applied. The obtained results confirmed the compatibility of the proposed network with the architecture of 20‐8‐2 (input‐hidden‐output) with the pattern model. It was concluded that analysis of blood samples by ATR‐FTIR spectroscopy and ANN chemometric technique would be a reliable approach for detection of BCC. Copyright © 2009 John Wiley & Sons, Ltd.
Functionalization of Dihalophenylboronic Acids by Deprotonation of Their N‐Butyldiethanolamine Esters
Authors: Durka Krzysztof , Kurach Paweł , Luliński Sergiusz , Serwatowski Janusz 
Published: July 2009

AbstractDeprotonative lithiation of various 6‐butyl‐2‐(dihalophenyl)‐(N–B)‐1,3,6,2‐dioxazaborocanes (N‐butyldiethanolamine esters of dihalophenylboronic acids) was investigated. It was found that selective transformations can be best achieved by use of LDA as the lithiating reagent. The reactivities of these compounds vary significantly, depending on the natures and positions of the halogen atoms. The resultant boron‐lithium bimetallic intermediates were subjected to reactions with electrophiles to afford functionalized halogenated arylboronic acids. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Enantiomeric separation by MEKC using dodecyl thioglycoside surfactants: Importance of an equatorially oriented hydroxy group at C‐2 position in separation of dansylated amino acids
Authors: Tano Chiharu , Son Sang‐Hyun , Furukawa Jun‐ichi , Furuike Tetsuya , Sakairi Nobuo 
Published: July 2009

AbstractTo investigate the influence of stereogenic centers of sugar‐based surfactants for enantiomeric separation, four n‐dodecyl thioglycoside sulfates (CMC 1.5–3.6 mM) were chosen as micelle‐forming surfactants and five dansylated hydrophobic amino acids were used as test analytes. The analytes were mutually separated by these micelles exhibiting almost similar migration times independent of the used surfactant. Baseline separations of all enantiomers were achieved using both β‐D‐glucose and β‐D‐galactose derivates that have an equatorially oriented hydroxy group at C‐2 position. In contrast, the ability of enantioseparation was markedly decreased in the case of β‐D‐mannose and 2‐deoxy‐β‐D‐glucose derivatives. These results suggested that the structure of C‐2 position of the sugar unit, namely presence of an equatorially oriented hydroxy group, is highly important for the enantiomeric separation of the chosen hydrophobic dansylated amino acids.
CE‐MS method development for peptides analysis, especially hepcidin, an iron metabolism marker
Authors: Martin Gaëlle B. , Mansion François , Servais Anne‐Catherine , Debrus Benjamin , Rozet Eric , Hubert Philippe , Crommen Jacques , Fillet Marianne 
Published: July 2009

AbstractA method for the resolution of a peptides mixture including hepcidin‐25, an iron metabolism marker, was developed by CE‐ESI‐MS. Several strategies were tested to optimize peptide separation, such as the addition of cyclodextrins or organic solvents in the BGE or the use of coated capillaries. Best results in terms of resolution, symmetry and efficiency were obtained with a BGE made of 500 mM ammonium acetate pH 4.5/ACN 70:30 v/v. Using the methodology of experimental design, BGE concentration, sheath liquid composition and MS‐coupling parameters were then optimized in order to obtain the best signal intensity for hepcidin. Finally, a 225 mM BGE and a sheath liquid composed of isopropanol/water 80:20 v/v containing 0.5% v/v formic acid were selected as it constitutes the best compromise for selectivity, peak shape and sensitivity.
Analysis of γ‐globulin mobility on routine clinical CE equipment: Exploring its molecular basis and potential clinical utility
Authors: Vanderschaeghe Dieter , Debruyne Evi , Van Vlierberghe Hans , Callewaert Nico , Delanghe Joris 
Published: July 2009

AbstractA study was conducted on the variability of γ‐globulin mobility in serum protein electrophoresis and its molecular basis. We found that the migration time of γ‐globulins can be reproducibly determined (CV=1.1%) on clinical CE equipment. Moreover, we found a significant difference (p<0.001) in the migration of γ‐globulins between chronic liver disease patients (n=98) and a healthy reference group (n=47). Serum immunoglobulins were purified from these patients' sera using protein L‐agarose and their glycosylation was studied using CE on a DNA sequencer. This glycomics approach revealed that several non‐sialylated N‐glycans show a moderate Pearson correlation coefficient (r=0.2–0.4) with the migration time of γ‐globulins. Their sialylated structures correlate negatively (r=−0.2 to −0.3). Immunoglobulins are significantly more sialylated in the healthy reference group compared with the patients (p<0.001). We estimated that sialylation heterogeneity contributes about 36% to the molecular variance (carbohydrates and amino acid composition) that affects the electrophoretic mobility of immunoglobulins. This is the first report on the migration time of γ‐globulins on a clinical CE instrument and its potential clinical value to the routinely analyzed serum protein CE profiles.
Vorinostat increases carboplatin and paclitaxel activity in non‐small cell lung cancer cells
Authors: Owonikoko Taofeek K. , Ramalingam Suresh S. , Kanterewicz Beatriz , Balius Trent E. , Belani Chandra P. , Hershberger Pamela A. 
Published: July 2009

AbstractWe observed a 53% response rate in non‐small cell lung cancer (NSCLC) patients treated with vorinostat plus paclitaxel/carboplatin in a Phase I trial. Studies were undertaken to investigate the mechanism (s) underlying this activity. Growth inhibition was assessed in NSCLC cells by MTT assay after 72 hr of continuous drug exposure. Vorinostat (1 μM) inhibited growth by: 17% ± 7% in A549, 28% ± 6% in 128‐88T, 39% ± 8% in Calu1 and 41% ± 7% in 201T cells. Vorinostat addition to carboplatin or paclitaxel led to significantly greater growth inhibition than chemotherapy alone in all 4 cell lines. Vorinostat (1 μM) synergistically increased the growth inhibitory effects of carboplatin/paclitaxel in 128‐88T cells. When colony formation was measured after drug withdrawal, vorinostat significantly increased the effects of carboplatin but not paclitaxel. The % colony formation was control 100%; 1 μM vorinostat, 83% ± 10%; 5 μM carboplatin, 41% ± 11%; carboplatin/vorinostat, 8% ± 4%; 2 nM paclitaxel, 53% ± 11%; paclitaxel/vorinostat, 46% ± 21%. In A549 and 128‐88T, vorinostat potentiated carboplatin induction of gamma‐H2AX (a DNA damage marker) and increased α‐tubulin acetylation (a marker for stabilized mictrotubules). In A549, combination of vorinostat with paclitaxel resulted in a synergistic increase in α‐tubulin acetylation, which reversed upon drug washout. We conclude that vorinostat interacts favorably with carboplatin and paclitaxel in NSCLC cells, which may explain the provocative response observed in our clinical trial. This likely involves a vorinostat‐mediated irreversible increase in DNA damage in the case of carboplatin and a reversible increase in microtubule stability in the case of paclitaxel.
Organic dyes as small molecule protein–protein interaction inhibitors for the CD40–CD154 costimulatory interaction
Authors: Buchwald Peter , Margolles‐Clark Emilio , Kenyon Norma S. , Ricordi Camillo 
Published: July 2009

AbstractIt is becoming increasingly clear that small molecules can often act as effective protein–protein interaction (PPI) inhibitors, an area of increasing interest for its many possible therapeutic applications. We have identified several organic dyes and related small molecules that (i) concentration‐dependently inhibit the important CD40–CD154 costimulatory interaction with activities in the low micromolar (µM) range, (ii) show selectivity toward this particular PPI, (iii) seem to bind on the surface of CD154, and (iv) concentration‐dependently inhibit the CD154‐induced B cell proliferation. They were identified through an iterative activity screening/structural similarity search procedure starting with suramin as lead, and the best smaller compounds, the main focus of the present work, achieved an almost 3‐fold increase in ligand efficiency (ΔG0/nonhydrogen atom = 0.8 kJ/NnHa) approaching the average of known promising small‐molecule PPI inhibitors (∼1.0 kJ/NnHa). Since CD154 is a member of the tumor necrosis factor (TNF) superfamily of cell surface interaction molecules, inhibitory activities on the TNF‐R1–TNF‐α interactions were also determined to test for specificity, and the compounds selected here all showed more than 30‐fold selectivity toward the CD40–CD154 interaction. Because of their easy availability in various structural scaffolds and because of their good protein‐binding ability, often explored for tissue‐specific staining and other purposes, such organic dyes can provide a valuable addition to the chemical space searched to identify small molecule PPI inhibitors in general. Copyright © 2009 John Wiley & Sons, Ltd.
VEGF‐D deficiency in mice does not affect embryonic or postnatal lymphangiogenesis but reduces lymphatic metastasis
Authors: Koch Marta , Dettori Daniela , Van Nuffelen An , Souffreau Joris , Marconcini Lucia , Wallays Goedele , Moons Lieve , Bruyère Françoise , Oliviero Salvatore , Noel Agnes , Foidart Jean‐Michel , Carmeliet Peter , Dewerchin Mieke 
Published: July 2009

AbstractVascular endothelial growth factor‐D (VEGF‐D) is one of the two ligands of the VEGFR‐3 receptor on lymphatic endothelial cells. Gene‐silencing studies in mice and Xenopus tadpoles recently showed that the role of endogenous VEGF‐D in lymphatic development is moderate. By contrast, exogenous VEGF‐D is capable of stimulating lymphangiogenesis. Nonetheless, its endogenous role in pathological conditions remains largely unknown. Hence, we reassessed its role in disease, using Vegf‐dnull mice. Vegf‐dnull mice were generated that, under physiological conditions, displayed normal embryonic and postnatal lymphangiogenesis and lymphatic remodelling, efficient lymphatic functioning and normal health. Vegf‐dnull mice also reponded normally in models of skin wound healing and healing of infarcted myocardium, despite enhanced expression of VEGF‐D in these models in wild‐type mice. In contrast, Vegf‐dnull mice displayed reduced peritumoral lymphangiogenesis and lymph node metastasis in an orthotopic pancreatic tumour model. Together, our data indicate that endogenous VEGF‐D in mice is dispensible for lymphangiogenesis during development, in postnatal and adult physiology and in several pathological conditions, but significantly contributes to lymphatic metastasis. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Familial small cell carcinoma of the ovary
Authors: Martinez‐Borges Anibal R. , Petty John K. , Hurt Gail , Stribling Jennifer T. , Press Joshua Z. , Castellino Sharon M. 
Published: July 2009

AbstractOvarian tumors have a low incidence in childhood, accounting for 1% of malignancies within the ages of 0–17 years. Small cell carcinoma of the ovary is a rare histology and historically has a poor prognosis. We report a case of an 11‐year‐old female diagnosed with small cell carcinoma of the ovary and hypercalcemia (SCCOHT). There was a strong family history of the disease, a reduction in the age of onset in the proband, and the absence of BRCA mutations. This case suggests the phenomenon of genetic anticipation in an ovarian cancer. Pediatr Blood Cancer 2009; 53:1334–1336. © 2009 Wiley‐Liss, Inc.
Lymphocytic vasculitis involving the central nervous system occurs in patients with X‐linked lymphoproliferative disease in the absence of Epstein–Barr virus infection
Authors: Talaat Kawsar R. , Rothman Jennifer A. , Cohen Jeffrey I. , Santi Mariarita , Choi John K. , Guzman Miguel , Zimmerman Robert , Nallasamy Sudha , Brucker Alexander , Quezado Martha , Pittaluga Stefania , Patronas Nicholas J. , Klion Amy D. , Nichols Kim E. 
Published: July 2009

AbstractX‐linked lymphoproliferative disease (XLP) is an immunodeficiency caused by defects in the adaptor molecule SAP. The manifestations of XLP generally occur following Epstein–Barr virus (EBV) infection and include fulminant mononucleosis, hypogammaglobulinemia and lymphoma. In this report, we describe two unrelated patients with fatal T‐cell‐mediated central nervous system vasculitis for whom repeated serologic and molecular testing for EBV was negative. In both patients, clonal T‐cell populations were observed, but neither demonstrated evidence of lymphoma. Thus, loss of SAP function can lead to dysregulated immune responses characterized by the uncontrolled expansion and activation of T cells independent of EBV infection. Pediatr Blood Cancer 2009;53:1120–1123. © 2009 Wiley‐Liss, Inc.
Natural history and outcome of optic pathway gliomas in children
Authors: Nicolin Gary , Parkin Patricia , Mabbott Donald , Hargrave Darren , Bartels Ute , Tabori Uri , Rutka James , Buncic J. Raymond , Bouffet Eric 
Published: July 2009

AbstractBackgroundThe optimal management of optic pathway gliomas (OPGs) is complicated by their variable natural history, the association with neurofibromatosis type 1 (NF1) and difficulties in defining progression and response to treatment.MethodsThis study is a retrospective review of all children presenting to a single institution with an OPG between 1990 and 2004.ResultsOf the 133 children included, 78 (59%) had NF1; 87 (71 NF1) were observed initially, of whom 23 (11 NF1) subsequently required treatment. Forty‐six patients received immediate treatment. Initial treatment, without or with an observation period, comprised chemotherapy alone (32, 11 NF1); debulking + chemotherapy (15, 4 NF1); gross total resection (6); radiotherapy (2); debulking + radiotherapy (3); and debulking only (12, 3 NF1). Overall, 16 patients were irradiated during the study period. Four children died (overall survival at 5 and 10 years was 97.6% and 94.6% for those who required treatment). Progression‐free survival (PFS) for the 69 patients who needed treatment was 48%. There was no difference in PFS between chemotherapy versus chemotherapy + debulking or debulking alone. PFS for the NF1 patients who required treatment was similar to that of non‐NF1 patients. Mean follow‐up time was 9.0 (range 0.6–18.0, median 8.6) years.ConclusionsThe study confirms the complexity of OPGs and that NF1 is a major determinant of the resultant behavior of the tumor. Pediatr Blood Cancer 2009; 53:1231–1237. © 2009 Wiley‐Liss, Inc.
Role of Wnt inhibitory factor‐1 and Wnt/wingless signaling in choroid plexus tumors
Authors: Tomm Manuel , Koch Arend , Mertsch Sonja , Wrede Brigitte , Jeibmann Astrid , Wolff Johannes , Paulus Werner , Hasselblatt Martin 
Published: July 2009

AbstractLittle is known on pathways involved in the pathogenesis of choroid plexus tumors (CPTs). The finding of overexpression of Wnt inhibitory factor‐1 (Wif‐1) prompted us to investigate the functional role of Wif‐1 as well as nuclear accumulation of beta‐catenin in CPT. In Z310 neoplastic choroid plexus epithelial cells, silencing of Wif1 expression increased proliferative activity not associated with increased canonical Wnt signaling. Nuclear beta‐catenin accumulation was also lacking in a series of 16 CPT. In conclusion, our data show that Wif‐1 inhibits proliferation of neoplastic choroid plexus epithelial cells, but argue against a role of canonical Wnt/wingless signaling in CPT. Pediatr Blood Cancer 2009;53:1152–1155. © 2009 Wiley‐Liss, Inc.
Trends in the prescription of anti‐diabetic medications in the United Kingdom: a population‐based analysis
Authors: Filion Kristian B. , Joseph Lawrence , Boivin Jean‐François , Suissa Samy , Brophy James M. 
Published: July 2009

AbstractPurposeOver the last decade, guidelines for the treatment of type 2 diabetes have increasingly favored tighter glycemic control, necessitating the use of more aggressive pharmacological therapy. The objective of this study was to describe trends in the prescription of anti‐diabetic medications among patients with type 2 diabetes in the United Kingdom (UK).MethodsUsing the General Practice Research Database, we constructed a cohort of patients with type 2 diabetes. Diabetes was defined as the presence of a diagnosis of diabetes, HbA1c ≥ 7%, or ≥ 2 prescriptions for anti‐diabetic medications. Analyses were conducted for the full cohort as well as a sub‐cohort with incident diabetes.ResultsOur full cohort involved 67 981 patients and a total of 320 089 patient‐years, and our sub‐cohort involved 30 234 patients with incident diabetes and 111 890 patient‐years. From 2000 to 2006, there was a substantial increase in the prescription rate of anti‐diabetic medications. Overall, there were 9.6 prescriptions/patient‐year in 2000, and this had increased to 14.8 prescriptions/patient‐year in 2006. The greatest relative increase occurred in the prescription of thiazolidinediones. The greatest absolute increase occurred in the prescription of metformin, which surpassed sulfonylureas as the most commonly prescribed anti‐diabetic medication among patients with type 2 diabetes in 2002. Among those with incident diabetes, overall prescription rates were 4.6 prescriptions/patient‐year in 2000 and 13.6 prescriptions/patient‐year in 2006.ConclusionsThere was a substantial increase between 2000 and 2006 in the UK in the prescription of anti‐diabetic medications. This increasingly aggressive pharmacological management is consistent with recent practice guidelines. Copyright © 2009 John Wiley & Sons, Ltd.
Accuracy analysis of multiple structure alignments
Authors: Berbalk Christoph , Schwaiger Christine S. , Lackner Peter 
Published: July 2009

AbstractProtein structure alignment methods are essential for many different challenges in protein science, such as the determination of relations between proteins in the fold space or the analysis and prediction of their biological function. A number of different pairwise and multiple structure alignment (MStA) programs have been developed and provided to the community. Prior knowledge of the expected alignment accuracy is desirable for the user of such tools. To retrieve an estimate of the performance of current structure alignment methods, we compiled a test suite taken from literature and the SISYPHUS database consisting of proteins that are difficult to align. Subsequently, different MStA programs were evaluated regarding alignment correctness and general limitations. The analysis shows that there are large differences in the success between the methods in terms of applicability and correctness. The latter ranges from 44 to 75% correct core positions. Taking only the best method result per test case this number increases to 84%. We conclude that the methods available are applicable to difficult cases, but also that there is still room for improvements in both, practicability and alignment correctness. An approach that combines the currently available methods supported by a proper score would be useful. Until then, a user should not rely on just a single program.
A Quantitative Structure‐Activity Relationship Study of Some Commercially Available Cephalosporins
Authors: Luan Feng , Liu Huitao , Gao Yuan , Guo Li , Zhang Xiaoyun , Guo Yun 
Published: July 2009

AbstractA quantitative structure‐activity relationship study of the binding of 28 commercially available cephalosporins to human serum proteins was performed with descriptors of molecular structure. Experimental data was the concentration of protein‐bound drug expressed as a percent of the total plasma concentration (percent fraction bound, PFB). A four parameter multiple linear correlation with squared correlation coefficients (R2) of 0.927 and root mean square error (RMS) of 8.67 is reported. The stability and predictive power of the models was verified by using the cross‐validation procedure. Polar interactions and the forming of hydrogen‐bonding properties are two major factors affecting the binding ability. The QSAR model presented is suitable for the rapid evaluation of PFB of cephalosporins.