bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Kinase Inhibitors Sunitinib and Sorafenib Differentially Affect NK Cell Antitumor Reactivity In Vitro
Authors: Krusch Matthias , Salih Julia , Schlicke Manuela , Baessler Tina , Kampa Kerstin Maria , Mayer Frank , Salih Helmut Rainer 
Published: December 2009

Abstract
Sunitinib and Sorafenib are protein kinase inhibitors (PKI) approved for treatment of patients with advanced renal cell cancer (RCC). However, long-term remissions of advanced RCC have only been observed after IL-2 treatment, which underlines the importance of antitumor immune responses in RCC patients. Because PKI, besides affecting tumor cells, also may inhibit signaling in immune effector cells, we determined how Sunitinib and Sorafenib influence antitumor immunity. We found that cytotoxicity and cytokine production of resting and IL-2-activated PBMC are inhibited by pharmacological concentrations of Sorafenib but not Sunitinib. Analysis of granule-mobilization within PBMC revealed that this was due to impaired reactivity of NK cells, which substantially contribute to antitumor immunity by directly killing target cells and shaping adaptive immune responses by secreting cytokines like IFN-γ. Analyses with resting and IL-2-activated NK cells revealed that both PKI concentration dependently inhibit cytotoxicity and IFN-γ production of NK cells in response to tumor targets. This was due to impaired PI3K and ERK phosphorylation which directly controls NK cell reactivity. However, while Sorafenib inhibited NK cell effector functions and signaling at levels achieved upon recommended dosing, pharmacological concentrations of Sunitinib had no effect, and this was observed upon stimulation of NK cell reactivity by tumor target cells and upon IL-2 treatment. In light of the important role of NK cells in antitumor immunity, and because multiple approaches presently aim to combine PKI treatment with immunotherapeutic strategies, our data demonstrate that choice and dosing of the most suitable PKI in cancer treatment requires careful consideration.
Inflammasome-Associated Nucleotide-Binding Domain, Leucine-Rich Repeat Proteins and Inflammatory Diseases
Authors: Jha Sushmita , Ting Jenny P.-Y. 
Published: December 2009

Abstract
The nucleotide-binding domain, leucine-rich repeat (NLR) proteins are a recently discovered family of intracellular pathogen and danger signal sensors. NLRs have emerged as important contributors to innate immunity in animals. The physiological impact of these genes is increasingly evident, underscored by the genetic association of variant family members with an array of inflammatory diseases. The association of mutations in NLR genes with autoinflammatory diseases indicates an important function of these genes in inflammation in vivo. This review summarizes the role of the inflammasome NLR proteins in innate immunity and inflammatory diseases and explores the possible utility of some of these NLRs as pharmacological targets.
Allele *1 of HS1.2 Enhancer Associates with Selective IgA Deficiency and IgM Concentration
Authors: Giambra Vincenzo , Cianci Rossella , Lolli Serena , Mattioli Claudia , Tampella Giacomo , Cattalini Marco , Kilic Sebnem S. , Pandolfi Franco , Plebani Alessandro , Frezza Domenico 
Published: December 2009

AbstractSelective IgA deficiency (IGAD) is the most common primary immunodeficiency, yet its pathogenesis is elusive. The IG (heavy) H chain human 3′ Regulatory Region harbors three enhancers and has an important role in Ig synthesis. HS1.2 is the only polymorphic enhancer of the 3′RRs. We therefore evaluated HS1.2 allelic frequencies in 88 IGAD patients and 101 controls. Our data show that IGAD patients have a highly significant increase of homozygousity of the allele *1 (39% in the IGAD patients and 15% in controls), with an increase of 2.6-fold. Allele *4 has a similar trend of allele *2, both showing a significant decrease of frequency in IGAD. No relationship was observed between allele *1 frequencies and serum levels of IgG. However, allele *1 was associated in IGAD patients with relatively low IgM levels (within the 30th lowest percentile of patients). The HS1.2 polymorphism influences Ig seric production, but not IgG switch, in fact 30th lowest or highest percentile of IgG in patients did not associate to different frequencies of HS1.2 alleles. The control on normal healthy subjects did not correlate high or low levels of IgM or IgG with HS1.2 allelic frequence variation. Overall our candidate gene approach confirms that the study of polymorphisms in human diseases is a valid tool to investigate the function of these Regulatory Regions that confers multiple immune features.
Involvement of the NLRP3 Inflammasome in Innate and Humoral Adaptive Immune Responses to Fungal β-Glucan
Authors: Kumar Himanshu , Kumagai Yutaro , Tsuchida Tetsuo , Koenig Paul A. , Satoh Takashi , Guo Zijin , Jang Myoung Ho , Saitoh Tatsuya , Akira Shizuo , Kawai Taro 
Published: December 2009

Abstract
Fungal β-glucan, such as curdlan, triggers antifungal innate immune responses as well as shaping adaptive immune responses. In this study, we identified a key pathway that couples curdlan to immune responses. Curdlan promoted the production of the proinflammatory cytokine IL-1β by dendritic cells and macrophages through the NLRP3 inflammasome. Stimulation with Candida albicans and Saccharomyces cerevisiae also triggered the NLRP3 inflammasome-mediated IL-1β production. In vivo, NLRP3 was required for efficient Ag-specific Ab production when curdlan was used as an adjuvant, whereas it was dispensable for the induction of Th1 and Th17 cell differentiation. Furthermore, stimulation of purified B cells with curdlan-induced CD69 up-regulation and IgM production while stimulation with other NLRP3 inflammasome activators, such as silica and aluminum salt, did not. Notably, this induction required NLRP3 but was independent of Toll-like receptor and IL-1 receptor family signaling, suggesting the presence of NLRP3-dependent and IL-1 receptor family independent mechanisms in B cells responsible for Ab responses. Collectively, these findings reveal a critical role for the NLRP3 inflammasome in the regulation of antifungal innate immune responses as well as B cell activation.
Dynamics of the Interaction of Human IgG Subtype Immune Complexes with Cells Expressing R and H Allelic Forms of a Low-Affinity Fcγ Receptor CD32A
Authors: Shashidharamurthy Rangaiah , Zhang Fang , Amano Aaron , Kamat Aparna , Panchanathan Ravichandran , Ezekwudo Daniel , Zhu Cheng , Selvaraj Periasamy 
Published: December 2009

AbstractCD32A, the major phagocytic FcγR in humans, exhibits a polymorphism in the ligand binding domain. Individuals homozygous for the R allelic form of CD32A (CD32AR allele) are more susceptible to bacterial infections and autoimmune diseases as compared with H allelic CD32A (CD32AH) homozygous and CD32AR/H heterozygous individuals. To understand the mechanisms behind this differential susceptibility, we have investigated the dynamics of the interaction of these allelic forms of CD32A when they are simultaneously exposed to immune complexes (IC). Binding studies using Ig fusion proteins of CD32A alleles showed that the R allele has significantly lower binding not only to human IgG2, but also to IgG1 and IgG3 subtypes. Competition assays using purified molecules demonstrated that CD32AH-Ig outcompetes CD32AR-Ig for IC binding when both alleles simultaneously compete for the same ligand. CD32AH-Ig blocked the IC binding mediated by both the allelic forms of cell surface CD32A, whereas CD32AR-Ig blocked only CD32AR and was unable to cross-block IC binding mediated by CD32AH. Two-dimensional affinity measurements also demonstrated that CD32AR has significantly lower affinity toward all three subtypes as compared with CD32AH. Our data suggest that the lower binding of CD32AR not only to IgG2 but also to IgG1 and IgG3 might be responsible for the lack of clearance of IC leading to increased susceptibility to bacterial infections and autoimmune diseases. Our data further suggests that in humans, inflammatory cells from CD32AR/H heterozygous individuals may predominantly use the H allele to mediate Ab-coated target cell binding during phagocytosis and Ab-dependent cellular cytotoxicity, resulting in a phenotype similar to CD32AH homozygous individuals.
Autoantibodies against C1q in Systemic Lupus Erythematosus Are Antigen-Driven
Authors: Schaller Monica , Bigler Cornelia , Danner Doris , Ditzel Henrik J. , Trendelenburg Marten 
Published: December 2009

AbstractAutoantibodies against complement C1q (anti-C1q Abs) were shown to strongly correlate with the occurrence of severe nephritis in patients with systemic lupus erythematosus (SLE), suggesting a potential pathogenic role by interfering with the complement cascade. To analyze the humoral immune response against C1q at the molecular level, we screened a bone marrow-derived IgGκ/IgGλ Fab phage display library from a SLE patient with high anti-C1q Ab titer against purified human C1q. Six Fabs that exhibited strong binding to C1q in ELISA were isolated. The anti-C1q Fabs recognized neoepitopes that were only exposed on bound C1q and not present on soluble C1q mapping to different regions of the collagen-like region of C1q. Analysis of the genes encoding the variable H and L chains of the IgG-derived anti-C1q Fab revealed that all the variable H and L chain regions were highly mutated, with nucleotide and amino acid homologies to the closest germline in the range of 71–97% (average 85 ± 4) and 72–92% (average 88 ± 6), respectively. In addition, the variable region of the Fabs exhibited high replacement to silent ratios. The six anti-C1q Fabs were shown to be of high affinity, with a Kd ranging from of 8.4 × 10−8 M to 1.4 × 10−7 M, comparable to an antiviral immune response. Our data underlines the notion that the development of anti-C1q Abs in SLE is the consequence of an Ag-driven, affinity-matured immune response. Those anti-C1q Fabs are unique tools to address how complement C1q is implicated in the pathogenesis of SLE.
Differential Responses to Smith D Autoantigen by Mice with HLA-DR and HLA-DQ Transgenes: Dominant Responses by HLA-DR3 Transgenic Mice with Diversification of Autoantibodies to Small Nuclear Ribonucleoprotein, Double-Stranded DNA, and Nuclear Antigens
Authors: Jiang Chao , Deshmukh Umesh S. , Gaskin Felicia , Bagavant Harini , Hanson Julie , David Chella S. , Fu Shu Man 
Published: December 2009

Abstract
Anti-Smith (Sm) D autoantibodies are specific for systemic lupus erythematosus. In this investigation, the influence of HLA-D genes on immune responses to SmD was investigated. Mice with HLA-DR3, HLA-DR4, HLA-DQ0601, HLA-DQ0604, or HLA-DQ8 transgenes were immunized with recombinant SmD1, and their Ab responses were analyzed. Analysis by ELISA showed that all strains responded well to SmD. However, when synthetic SmD peptides were used as substrate, DR3 mice had the highest Ab response followed by DQ8, DQ0604, DQ0601, and DR4. A similar trend was observed in Western blot analysis using WEHI 7.1 cell lysate as the substrate, with the exception that DR4 mice did not generate detectable amounts of Abs. Only sera from DR3 and DQ0604 mice immunoprecipitated A-ribonucleoprotein (RNP), SmB, and SmD. Intermolecular epitope spreading to A-RNP and SmB was evident in DR3 and DQ0604 mice, as sera depleted of anti-SmD Abs were reactive with these proteins. DR3 mice also generated an immune response to C-RNP. Anti-nuclear Abs were detected in the majority of the DR3 mice, whereas moderate reactivities were seen in DQ0604 and DQ8 mice. Interestingly, only DR3 mice mounted an anti-dsDNA Ab response. Approximately half of the anti-dsDNA Abs were cross-reactive with SmD. Ab responses correlated with the strength of the T cell responses. Thus, HLA-DR3 appears to be the dominant HLA-D gene that determines the magnitude and quality of the anti-SmD immune response. In addition, our findings provide insights into the origin of the anti-dsDNA Abs often detected in patients with systemic lupus erythematosus.
Serum potassium, calcium and magnesium in patients receiving ESHAP chemotherapy for relapsed lymphomas
Authors: Zekri J , Cheah NLC , Evans L , Hancock B 
Published: December 2009

Etoposide, methylprednisolone, cytarabine and cisplatin (ESHAP) is one of the mostly widely used chemotherapy regimens for patients with relapsed lymphomas. Cisplatin administration is commonly associated with electrolyte imbalance. Careful monitoring of renal function and serum electrolytes is therefore essential in this setting. Aims: To review the practice of electrolyte monitoring – potassium (K), calcium (Ca) and magnesium (Mg) – in patients receiving ESHAP and the frequency and severity of abnormalities and their management. Methods: Twenty-one consecutive patients received ESHAP. The medical records of 16 patients were retrievable and reviewed retrospectively. Results of serum K, Ca and Mg were collected prior to and after cycles 1, 2 and 3 of ESHAP, if measured. Results: Serum K levels prior to every cycle did not show any noticeable change. The means were 4.42, 4.34 and 4.43 mmol/l before cycles 1, 2 and 3, respectively. In one patient hypokalaemia was severe, refractory and symptomatic when preceded by hypomagnesaemia. Serum-adjusted calcium levels showed only minimal reduction. The means were 2.46, 2.40 and 2.38 mmol/l before cycles 1, 2 and 3 respectively. Mean serum Mg levels prior to every cycle showed progressive reduction; 0.84, 0.75 and 0.67 mmol/l before cycles 1, 2 and 3, respectively. This was associated with a progressive increase in the amount of required Mg supplementation. Serum K, Ca and Mg was measured prior to 100%, 67% and 35% of administered cycles, respectively. Conclusion: In patients receiving ESHAP, hypokalaemia can occasionally be seen, especially if preceded by hypomagnesaemia. Mild cumulative hypocalcaemia is recognised. Hypomagnesaemia is a progressive complication and physicians need be aware of its importance.
Nonenzymatic Oligomerization of Activated Nucleotides on Hairpin Templates
Authors: Kim Eun‐Kyong , Switzer Christopher 
Published: December 2009

AbstractThis unit describes a protocol for nonenzymatic oligomerization of activated ribonucleotides on DNA hairpins appended by templates containing threofuranosyl nucleic acid (TNA). TNA‐cytidylate templates effectively promote oligomerization of 2‐MeImpG, and give 3′,5′‐linked oligomerization products predominantly, with good base‐pairing fidelity. Although the rates of oligomerization depend on TNA content, after 3 days of incubation, oligomerization products are apparent, and full‐length products are present after 10 days. Characterization of product phosphodiester bond regiochemistry is accomplished by digestion with RNase T1. Additionally, exposure of oligomerization products to calf intestinal alkaline phosphatase enables detection of any endcapping due to pyrophosphate formation. Base‐pairing fidelity is assessed by challenging the template to oligomerize 2‐MeImpA. The protocols described for nonenzymatic, template‐directed synthesis in this unit are applicable to oligomerization of activated monomers on templates of different compositions, with respect to both base identity and polymer backbone. Curr. Protoc. Nucleic Acid Chem. 39:3.18.1‐3.18.13. © 2009 by John Wiley & Sons, Inc.
Fluorescence Correlation Spectroscopy in Living Cells: A Practical Approach
Authors: Altan‐Bonnet Nihal , Altan‐Bonnet Grégoire 
Published: December 2009

AbstractFluorescence correlation spectroscopy (FCS) is a single‐molecule fluorescence technique used to monitor molecular dynamics. It can be applied to living cells expressing fluorescently labeled proteins and lipids to determine the diffusion timescales and the total number of diffusing fluorescent molecules in the cell. A practical step‐by‐step approach to performing FCS with a commercial spectroscopy/microscopy system, the Zeiss Confocor 3, how to set up live‐cell FCS experiments, acquire reliable data, and finally how to analyze the data acquired, are all described in this unit. Curr. Protoc. Cell Biol. 45:4.24.1‐4.24.14. © 2009 by John Wiley & Sons, Inc.
Generation of Micropatterned Substrates Using Micro Photopatterning
Authors: Doyle Andrew D. 
Published: December 2009

AbstractMicro photopatterning (µPP) has been developed to rapidly test and generate different patterns for extracellular matrix adsorption without being hindered by the process of making physical stamps through nanolithography techniques. It uses two‐photon excitation guided through a point‐scanning confocal microscope to locally photoablate poly(vinyl) alcohol (PVA) thin films in user‐defined computer‐controlled patterns. PVA thin films are ideal for surface blocking, being hydrophilic substrates that deter protein adsorption and cell attachment. Because gold substrates are not used during µPP, all live‐cell fluorescent‐imaging techniques including total internal reflection fluorescence microscopy of GFP–linked proteins can be performed with minimal loss of fluorescence signal. Furthermore, because µPP does not require physical stamps for pattern generation, multiple ECMs or other proteins can be localized within microns of each other. This unit details the setup of µPP. It also provides troubleshooting techniques. Curr. Protoc. Cell Biol. 45:10.15.1‐10.15.35. © 2009 by John Wiley & Sons, Inc.
Microstructural behaviors of polyaniline/CB Composites by SAXS
Authors: Siddaramaiah  , Souza Fernando G. , Soares Bluma G. , Parameswara P. , Somashekar R. 
Published: December 2009

AbstractPolyaniline doped with dodecylbenzene sulfonic acid and conductive carbon black (PAn.DBSA/CB) hybrid materials have been prepared by in situ polymerization. The electrical resistivity of the PAn/CB was measured as a function of CB. The minimum resistivity was noticed for the composites with 25 wt % of CB as compared to other systems. Small angle x‐ray diffraction data was used to characterize the molecular arrangements of these composites. The refinement parameters such as periodicity (L), phase lengths (<Y> and <Z>), phase ratio (<Y>/<Z>), and probability distribution of phases [γZ (crystalline), γY (amorphous)] for PAn, CB, and PAn/CB composites have been measured by SAXS data. It was observed that there is decrease in the crystallinity with increase in CB content in the composites. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2010
Synthesis and characterization of polyaniline/silica doped with camphorsulfonic acid and dodecylbenzylsulfonic acid
Authors: Lee Hsun‐Tsing , Yang Shung‐Jim 
Published: December 2009

AbstractIn this study, the effect of the dopant structure on the morphology, structure, optical absorption, conductivity, and thermal properties of conductive polyaniline (PAn)/silica (SiO2) hybrids from a sol–gel process was first investigated. Camphorsulfonic acid (CSA) and dodecylbenzylsulfonic acid (DBSA) were used as the model acid dopants. The polaron absorption peaks of the CSA‐doped PAn/SiO2 (CSA–PAn/SiO2) hybrids were redshifted compared with those of the DBSA–PAn/SiO2 hybrids. This indicated that the doped PAn subchains of the CSA–PAn/SiO2 hybrids had a more rigid conformation and longer conjugation length than those of DBSA–PAn/SiO2 hybrids. Therefore, the CSA–PAn/SiO2 hybrids were more conductive than the DBSA–PAn/SiO2 hybrids with same SiO2 contents. Moreover, the CSA–PAn/SiO2 hybrids exhibited higher SiO2 condensation degrees and thermal resistance than the DBSA–PAn/SiO2 hybrids with same SiO2 contents. In addition, the CSA–PAn/SiO2 films exhibited a nonuniform globular morphology, whereas the DBSA–PAn/SiO2 films showed an interconnected and rugged fibrillar one. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2010
Semantic annotation of biosystematics literature without training examples
Authors: Cui Hong , Boufford David , Selden Paul 
Published: December 2009

AbstractThis article presents an unsupervised algorithm for semantic annotation of morphological descriptions of whole organisms. The algorithm is able to annotate plain text descriptions with high accuracy at the clause level by exploiting the corpus itself. In other words, the algorithm does not need lexicons, syntactic parsers, training examples, or annotation templates. The evaluation on two real‐life description collections in botany and paleontology shows that the algorithm has the following desirable features: (a) reduces/eliminates manual labor required to compile dictionaries and prepare source documents; (b) improves annotation coverage: the algorithm annotates what appears in documents and is not limited by predefined and often incomplete templates; (c) learns clean and reusable concepts: the algorithm learns organ names and character states that can be used to construct reusable domain lexicons, as opposed to collection‐dependent patterns whose applicability is often limited to a particular collection; (d) insensitive to collection size; and (e) runs in linear time with respect to the number of clauses to be annotated.
Analysis of phenolic compounds in health care products by low‐pressure liquid‐chromatography with monolithic column and chemiluminescent detection
Authors: Ballesta‐Claver J. , Valencia M. C. , Capitán‐Vallvey L. F. 
Published: December 2009

AbstractThis paper presents a new application for monolithic columns with low‐pressure chromatographic separation using an flow injection analysis configuration with chemiluminescent detection for the determination of a mixture of phenolic compounds: phloroglucinol, 2,4‐dihydroxybenzoic acid, salicylic acid, methyl paraben and n‐propyl gallate. The procedure consists of the separation of these compounds on a reverse‐phase ultra‐short monolithic column with pH 3.0 acetate buffer and 5% acetonitrile as carrier phase. The detection is based on a chemiluminescence measurement coming from Ce(IV)–Rhodamine 6G chemistry with the incorporation of two different chemiluminescent chemical conditions in the chromatographic setup in order to enhance the sensitivity for the different phenolic compounds. All separation and detection variables were optimized to propose a determination method. The analysis is performed in 280?s, with the sampling frequency being some 13 h−1. The calibration function is a double reciprocal function obtaining good results within two orders of magnitude. The limits of detection were 8.8 × 10 −8 m (phloroglucinol), 2.7 × 10 −8 m (2,4‐dihydroxybenzoic acid); 2.3 × 10 −8 m (salicylic acid); 5.2 × 10 −8 m (methyl paraben) and 4.1 × 10 −6 m (n‐propyl gallate), and the relative standard deviations at a medium level of the linear range were 4.4% (phloroglucinol), 2.8% (2,4‐dihydroxybenzoic acid), 5.2% (salicylic acid), 3.6% (methyl paraben) and 6.8% (n‐propyl gallate). The method was applied and validated satisfactorily for the determination of these compounds in healthcare products, comparing the results against an HPLC reference method. Copyright © 2009 John Wiley & Sons, Ltd.